Author: acrf

Researchers at The Australian National University (ANU) have discovered how a DNA-binding protein sustains Hodgkin lymphoma.

The world-first discovery has the potential to help treat the rare cancer with the development of therapeutics that target cells once they become cancerous. The findings are published in EMBO Reports.

Approximately 800 Australians are diagnosed with Hodgkin lymphoma per year. The disease causes cancer in white blood cells, called lymphocytes, in men and women of any age, but young people in particular.

The research team discovered the histone protein, H2A.B that is normally active only in the testes and the brain, becomes abnormally activated in lymphocytes, stimulating conditions that sustain Hodgkin lymphoma. 

Lead researcher Dr Tanya Soboleva, from the ANU John Curtin School of Medical Research (JCSMR), said the discovery could hold the key to better health outcomes for thousands of patients globally.

“H2A.B. is an incredibly powerful protein. It binds to DNA and controls it in multiple ways including activation of genes that are known to promote cancer,” Dr Soboleva said.

“Histone proteins like H2A.B can package two meters of DNA into a cell that is only 20-micron in diameter. That is the same as packing a rope that is the diameter of a football field into a football.

“With H2A.B being active, the DNA packaging becomes less tight, making DNA more susceptible to the activity of cancer-driving proteins.

“In our study, we found that H2A.B becomes abnormally activated in all types of Hodgkin lymphoma and we have found the mechanism by which H2A.B drives cancer. Essentially, the protein stimulates cells in such a way that they grow and divide more readily.

“This is the first time it has been shown how a testis- and brain-specific protein can drive cancerous processes when it becomes active in the wrong cell type.

“Now that we have identified this protein and the role it plays in making cells cancerous, we think we can target it to stop this from happening.

“For example, our study shows that when we deplete H2AB quantities in Hodgkin lymphoma cells grown in a flask in the lab, the cells stop growing well.”

“Our discovery is really exciting. For the first time, we have the opportunity to target H2A.B only within Hodgkin lymphoma cells and spare all other cell types in our body,” Dr Soboleva said.

“Most cancer therapeutics aren’t currently able to do this.

“Besides new hope for those who suffer from Hodgkin’s lymphoma, these therapeutics could also work for those suffering other types of lymphoma and breast cancer.”

This research was undertaken by ANU PhD graduate Dr Xuanzhao Jiang; JCSMR bioinformatician, Dr Jiayu Wen; senior pathologist at the Canberra hospital, Professor Jane Dahlstrom; and was co-led by Professor David Tremethick from JCSMR.

This article originally appeared on the John Curtin School of Medical Research website. ACRF has backed $2.13 Million of Brilliant Cancer Research at JCSMR.

Women recovering from endometrial cancer require health professionals to provide them with individualised weight management plans to assist with their recovery, a University of Queensland study has shown.

UQ’s Professor Monika Janda said endometrial cancer was the most common sub-type of womb cancer and survivors often had issues with obesity and weight gain before and following treatment.

“Being obese or overweight is a major risk factor for endometrial cancer and even nine years after surgery, we found that the vast majority of the women were not content with their current weight,” Professor Janda said.

This topic is important for women as they also have an increased risk of cardiovascular disease, diabetes, and other chronic health conditions if they’re overweight.

The study investigated weight perceptions among long-term endometrial cancer survivors and what weight control methods women used.

“We asked what weight management plans they followed and they had tried all kinds of different diets that you can think of, except very few tried fasting,” Professor Janda said.

“Findings from this study suggest there is a need for health professionals and lifestyle educators to develop tailored and individualised diet and weight management plans to address the specific needs of long-term survivors following treatment for endometrial cancer.

“One of the key activities in this research was to investigate why they found it so hard to lose weight and how this could be made easier.

“They suggested that it would be good to have peer support or counselling at the time of surgery – someone who had been through the same process to support them.”

The study surveyed 259 women who were on average nine years post-surgery.

Professor Janda, who leads the Behavioural Science Unit at UQ’s Centre for Health Services Research, said the data in the current paper was a long-term follow-up of an original trial with 760 women.

“The original trial was a surgical trial which compared open abdominal surgery with laparoscopic surgery, which is keyhole surgery,” she said.

“That trial showed that laparoscopic surgery gives women better quality of life, we then followed these women to determine who still had adverse events following their laparoscopic surgery.

“We found that the women who were overweight or obese were at greater risk of complications after surgery, so we asked them in the follow-up what they do about weight loss, and that is what inspired this new paper.”

This article originally appeared on the University of Queensland Website. ACRF has given five grants of in total $17.4 Million to the University of Queensland for life-saving cancer research.

In 2015, Australian Cancer Research Foundation awarded a $2 million grant to the Australian Synchrotron for a detector that analyses the shape and function of proteins on the Institute’s Micro Crystallography (MX2) beamline. Thanks to this funding, this process is now delivered in a fraction of the time it took previously – a ten-fold increase in capacity, crucial to accelerating cancer drug development. This has been made possible by the generosity of our ACRF community.

The Australian Synchrotron houses two beamlines with complementary capabilities, MX1 and MX2.  

MX1 facilitates high-density throughput screening.MX2,with its upgraded ACRF Detector, is ideal for weakly-diffracting hard-to-crystallise proteins, viruses, protein assemblies and nucleic acids – as well as smaller molecules such as inorganic catalysts and organic drug molecules. 

In 2020, the ACRF Detector collected 46,683,192 diffraction images, associated with 56,045 datasets across 208 distinct group experiments, leading to advances in the understanding and potential treatment of cancers. 

These advances included the first building block of a drug to target acute myeloid leukaemia (AML) and a discovery that will pave the way for developing improved therapies for a range of cancers. 

• Targeting AML: Researchers at the Peter MacCallum Cancer Centre, using the ACRF Detector at the Synchrotron found a way to target AML, an aggressive and often incurable cancer. The protein HBO1 is essential for the survival of leukemic stem cells, likely to be the main cause for resistance to current AML treatments. 
   
  The research team undertook a series of experiments to discover the part of the HBO1 protein that was critical for its function in stem cells and then developed a small molecule – the first building block of a drug – that could suppress the activity of HBO1 in AML cells. 
   
• A model for the development of new cancer treatments: A study by Monash Biomedicine Discovery Institute researchers highlights the synergy between an antibody fragment that acts as a bridge helping to link together two key immune cell receptors. It also takes advantage of their interaction, enabling the body to enhance its immune response to cancer. This discovery will serve as a model for the potential development of new, improved therapies against a broad range of cancers. 

In 2020, 204 peer-reviewed journal publications were produced, containing data from the MX1 and MX2 beamlines, with a substantial proportion of these (~50%) published in high-impact journals. 

Significantly, 152 of 480 protein structure deposits into the Worldwide Protein Bank were specifically from research undertaken using the ACRF Detector. 

Research undertaken using the ACRF Detector continues to inform and assist cancer research as it expands the store of knowledge on protein structures, biomolecular processes and structural determination methods. 

Thank you to all our generous supporters who continue to make progress like this possible. Together we can make a world without cancer a reality.

Researchers investigating a group of microscopic cells have discovered they can put the brakes on the rapid development of melanoma lesions.  

A team at WEHI, in collaboration with the University of Queensland and the Peter MacCallum Cancer Centre, have taken a close look at the relatively recently identified Group 2 innate lymphoid cells (ILC2) which are crucial for initiating and orchestrating immune responses.

UQ Diamantina Institute’s Professor Gabrielle Belz said their aim was to understand more about the function of these relatively recently identified cells and their roles in melanoma.

“We wanted to investigate how ILC2 contribute to melanoma formation, because we already knew these cells harboured functions that could either suppress or stimulate production of cancerous tumours,” Professor Belz said.

“Previously, we understood very little about the underlying mechanisms of these intriguing cells, and whether they could be clinically relevant or targeted to apply the brakes on melanoma development.

“We discovered these cells can halt the rapid development of full-blown melanoma lesions and can potentially be harnessed to drive protective functions with potential immunotherapy applications.”

At a glance

• Researchers have taken a close look at the Group 2 innate lymphoid cells (ILC2) which are crucial for initiating and orchestrating immune responses.
• They discovered the ILC2 cells can halt the rapid development of melanoma lesions and can potentially be harnessed to drive protective functions with potential immunotherapy applications.
• This opens a new pathway to explore targets not previously used as part of immunotherapy treatments, to both prevent development of metastasis and prevent resistance to therapy.

Enhancing anti-tumour activity

Approximately two thirds of Australians will be diagnosed with a form of skin cancer before they are 70 years of age, and Australia and New Zealand have the highest rates of melanoma in the world.

WEHI’s Dr Cyril Seillet the research found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis.

“We found that ILC2 within tumours express the immune checkpoint inhibitor PD-1. We could enhance the anti-tumour activity of ILC2 with an existing cancer immunotherapy that blocks PD-1 interactions,” he said.

“ILC2s are also critical producers of a colony-stimulating factor known as GM-CSF, which coordinates the recruitment and activation of a type of disease-fighting white blood cell called eosinophils.”

“Our results identified not only that ILC2s have a critical function in melanoma immunity, but also that there was a potentially coordinated approach to harness ILC2 function for anti-tumour immunotherapies.

“Science underpins healthcare, and this opens a new pathway to explore targets not previously used as part of the immunotherapy regime, to both prevent development of metastasis and prevent resistance to therapy.”

Hope for new treatments

Dr Nicolas Jacquelot, who helped lead the study at WEHI and is now at the Princess Margaret Cancer Centre in Canada, said the findings were promising.

“This shows our capacity to further increase immune responses against melanoma and the possibility to develop new immunotherapy strategies to boost the ILC2-eosinophil axis to fight tumour cells,” Dr Jacquelot said.

“This gives us real hope for improving outcomes for patients.”

Associate Professor Paul Neeson said the team at Peter Mac and the collaborative Centre for Cancer Immunotherapy was able to clinically validate the findings in human skin and, in particular, cases of melanoma.

“Our team showed these rare immune cells (ILC2) were present in human melanoma samples – both when patients were first diagnosed, and in patients with advanced disease,” Dr Neeson said.

This work was made possible with support from the National Health and Medical Research Council and the Victorian Government.

This article originally appeared on the WEHI website. In 2018, ACRF granted $9.9 Million to UQ’s Diamantina Institute for cutting-edge melanoma research thanks to the generosity of our supporters.

During the past year, COVID-19 has taught us to appreciate the significant impact that viruses can have on our health and well-being.  Human health can be impacted by many different types of virus with some causing diseases such as the common cold (rhinovirus), influenza, rabies and poliomyelitis.  

The potential impact of viruses can be avoided or minimised by a person’s general good health, strength of the immune system, favourable genetics, avoidance of sources of infection and immunisation.  However, on rare occasions, viral infections have been shown to lead to cancer.

Oncogenic viruses (viruses that can cause cancer) act by integration of their DNA into the host cell.  This can lead to the development of cancer in a variety of ways, such as when these viral oncogenic genes impair the functioning of two families of tumour suppressor proteins, namely p53 and retinoblastoma proteins (Rb).  

P53 and Rb are involved in controlling the cell division cycle by allowing time for damaged or altered DNA to the repaired and, if repair is not possible, to initiate programmed cell death or apoptosis.  Interference or disabling p53 and/or Rb can instigate uncontrolled cell division leading to cancer.  In addition, the cancer may arise through the action of the oncogenic virus leading to the suppression or disruption of the immune system or by the viral infection causing long-term or chronic inflammation in the susceptible organ or tissue.

In 2002 the World Health Organisation estimated that about 18% of human cancers were caused by viral infections and with the majority attributed to only seven viruses.  

1. Human papillomavirus (HPV) – there are more than 200 types of HPV, with 14 high-risk types including HPV 16 and HPV 18.  Transmission is through skin-to-skin contact and has been shown to cause cancer of the cervix, vagina, vulva, penis, anus and oropharynx.  Supporters like you contributed to the seed funding for Professor Ian Frazer’s development of a cervical cancer vaccine which protects against HPV 16 and HPV 18. Thanks to a national immunisation program, Australia is set to be the first country to effectively eliminate the disease.
2. Epstein-Barr virus (EPV) – this herpes type virus is usually associated with mononucleosis or glandular fever and is spread through bodily fluids such as saliva and blood.  EPV can lead to mutations that contribute to certain rare cancers, such as Burkitt’s lymphoma, nasopharyngeal cancer and Hodgkin’s lymphoma.  
3. Hepatitis B virus (HBV) – spread through sharing bodily fluids.  Chronic HBV infection leads to liver inflammation and damage that are risk factors for liver cancer. 
4. Hepatitis C virus (HCV) – less likely to show symptoms than HBV but with a higher incidence of chronic infection.  HCV is associated with liver inflammation and damage which are risk factors for liver cancer.
5. Human herpes virus 8 (HHV-8) – transmitted through saliva.  Infections are rare and can particularly impact on people with a weakened immune system.  HHV-8 has been associated with Kaposi sarcoma.  
6. Human T-lymphotrophic virus (HTLV) – a retrovirus that is spread through blood transfers, breast milk and semen.  There are no symptoms but HTLV is associated with acute T-cell leukaemia/lymphoma.
7. Merkel Cell polyomavirus (MCV) – potential skin-to-skin transmission with no symptoms.  MCV is associated with Merkel Cell carcinoma, a rare type of skin cancer. 

The prevention of viral cancers has found success in utilising vaccines to stimulate the body’s immune system to block infection.  The Hepatitis B vaccine was the first vaccine recognised for its ability to help reduce the risk of liver cancer.  The HPV vaccine (Gardasil) was approved by the FDA in 2006 to prevent cervical cancer in adolescent girls.  Hundreds of millions of doses of Gardasil have been used in many countries around the world in preventative campaigns.  Subsequent research has shown it to be effective in reducing the incidence of a number of other genital cancers in both boys and girls.  The current version, Gardasil 9, protects against nine types of HPV including seven of those posing the highest risk.

Apart from vaccines the prevention of viral infections is best achieved through good hygiene, hand washing, not sharing personal items, using barrier protection during sexual activity and screening for viral infections such as HCV. 

This article was written by Dr Ian Brown, ACRF Chief Scientific Officer.

Researchers at Children’s Medical Research Institute (CMRI) have published in Clinical Epigenetics about a protein found to play an important role in cancer cell division. The research found that by depleting the BRG1 protein in cancer cells, genes involved in DNA replication were repressed. This finding reveals new insight into how cancer cells spread and hints at new drug targets in cancer treatment.

The research was the brainchild of Dr Kate Giles in the Genome Integrity unit at CMRI, who started looking at the BRG1 protein eight years ago. “The initial work, performing RNA sequencing on prostate cancer tissue, was performed as part of my PhD in 2014, so this has been a long journey and it’s great to see it complete and published,” Dr Giles said. “There have been four or five studies on the over-expression of BRG1 in cancers, but our research is different because we’re looking at why this overexpression of BRG1 matters. We wanted to know what it does.”

Dr Giles and her fellow researchers used prostate cancer samples to examine the pathways within a cell that were affected by BRG1. They found that certain genes behaved differently in the presence of BRG1, and all these genes had a role in cell division. Once they knew that which genes were affected by BRG1, the researchers depleted BRG1 and found it inhibited cell division.

This action of the BRG1 protein comes under what biologist call ‘epigenetics’. Epigenetics is the study of how the same base genetic information in DNA can produce different outcomes in different cells. While our DNA remains the same in every cell, genes can be turned on, turned off, or repressed by proteins present in the cell. The protein BRG1, part of the larger SWI/SNF protein (pronounced swee-sniff), makes physical changes to the scaffolding on which genetic information sits (chromatin remodelling), altering which genetic information is ‘accessible’ and which proteins are able to be produced.

“We can think of DNA as a paragraph of text on a page with all the core information about a person,” Dr Giles explained. “Epigenetics is like the punctuation, the highlighting, and the crossing-out which gives different emphasis to the text. Through epigenetic processes, the same core text can be read differently in different cells or under different conditions. We can highlight text that is particularly important to a cell, or we could redact certain words or phrases. These changes can turn genes on or off in specific cells.”

Moving to CMRI was able to help Dr Giles understand why the overexpression of BRG1 was important in cancer cells.

“Confirming the functional effect of BRG1 has been the majority of my research here at CMRI. Coming to CMRI was where the research took off because of the particular expertise of the people here. Being able to collaborate with colleagues who were experts in cell cycle processes was particularly helpful.”

Dr Giles speculated on BRG1 as a target for cancer drug treatments. “BRG1 would be a nice target for certain leukaemias and some breast cancers. Unfortunately, at the moment there are only two drug inhibitors of BRG1, and the part of the protein they target doesn’t completely stop its function.”

Dr Giles was optimistic on the future of epigenetic research and, in particular, of the importance of chromatin remodelling research. “I do really like this type of research. I’m really glad that it’s led to the project I’m working on now at CMRI. Chromatin remodelling can sometimes be overlooked, but we think that’s changing.”

This article originally appeared on the CMRI website. ACRF has granted $12 Million to CMRI for world-class cancer research.

A WA discovery made global news when venom from honeybees was found to kill aggressive breast cancer cells.

Associate Professor and Wesfarmers Fellow, Dr Pilar Blancafort, from the Harry Perkins Institute of Medical Research, co-published these findings with her PhD student Dr Ciara Duffy and laboratory co-workers a few months ago.

Their results revealed that honeybee venom rapidly destroyed triple-negative breast cancer and HER2-enriched breast cancer cells.

Dr Blancafort says this discovery was inspired by nature.

“In discovery-based research, we go to mother nature to understand what it does. This is the importance of the biomedical research that we do in our laboratory – we take something that exists in nature and apply it to target hard-to-treat cancers and other diseases,” says Dr Blancafort.

Dr Blancafort believes you should travel the world and place yourself in uncomfortable situations to free yourself up to discover new things. She feels that this is the essence of discovery.

“You truly start from scratch in discovery research with no precedent, so there is an inherent risk – but you have to try in order to reach the impact needed to solve biological problems, such as those in cancer biology. I have always learned so much from moving away from the same place, to explore the world, and free myself to think in other directions. The answer is there, somewhere,” says Dr Blancafort.

No-one had previously compared the effects of a small peptide named melittin, found in the honeybee venom, across the different subtypes of breast cancer and normal cells. Dr Duffy, under Dr Blancafort’s supervision, tested the venom on normal breast cells and found that it was extremely potent.

“We found that melittin can completely destroy cancer cell membranes within 60 minutes and substantially reduced the chemical messages of cancer cells that are essential to growth and cell division,” says Dr Blancafort.

The team is also keen to investigate melittin’s applicability to other diseases such as ovarian cancer.

While it’s early days, the laboratory work is deemed significant – suggesting melittin might help develop better-targeted treatment for breast and other cancers. However, it’s a long process from bench to bedside with numerous steps over several years required before development of commercial treatments can occur.

“The next steps require a multidisciplinary collaboration and a significant investment of resources,” says Dr Blancafort.

“We are grateful for our community of loyal supporters. They’re crucial because they support the early discovery part of the research and donate to the ongoing exploration.

“We need funding to help take our research from where we are now to where we want to be. We’re curious and willing to take the risk, and looking forward to collaborating with others who value the impact we can make in the community.

Professor Peter Leedman, Director of Harry Perkins Institute of Medical Research and 2021 recipient of an Officer of the Order of Australia says, “This is an incredibly exciting observation that melittin can suppress the growth of deadly breast cancer cells.

“Triple-negative breast cancer and other hard-to-treat cancers are a major focus for researchers at the Perkins.

“We thank all our supporters in the WA community who make our research possible.”

This article originally appeared on the Harry Perkins Institute of Medical Research Website. ACRF has given $1.75 Million to Harry Perkins for cancer research equipment.

Researchers from QIMR Berghofer Medical Research Institute have developed a prototype test that can help identify if patients with deadly metastasised melanoma are likely to benefit from immunotherapy.

Details about the test and the study have been published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

The prototype test detects levels of the protein LC3B on cancer cells. High levels of LC3B are associated with better patient responses to a form of treatment known as checkpoint inhibitor immunotherapy.

Metastatic melanoma is a very aggressive disease and according to the Australian Institute of Health and Welfare, 1,375 Australians died from it in 2020.

Most patients undergo surgery and almost all patients with metastatic melanoma are now given immunotherapy as a standard frontline treatment.

Lead researcher Associate Professor Jason Lee, who heads QIMR Berghofer’s Epigenetics and Disease group, said immunotherapies have remarkably improved treatment and survival rates for metastatic melanoma, but more than half of all patients do not respond.

“We need to treat these patients quickly and with the correct kinds of drugs to have any success,” Associate Professor Lee said.

“Our study found patients with high levels of LC3B in their tumour cells had significantly longer survival due to better responses to immunotherapy treatment than those with lower levels. The study showed 95 per cent of patients with high LC3B levels were alive after 3 years, compared to 60 per cent of patients with low LC3B levels.”

The researchers used tumour and blood samples collected from melanoma patients before and after treatment to get a better understanding of the role of the LC3B protein in metastatic melanoma and to develop the prototype test.

PhD candidate in QIMR Berghofer’s Epigenetics and Disease group, Greg Kelly, said they also identified that patients with metastatic melanoma had very high levels of the epigenetic enzyme G9a – which acts on LC3B protein.

“The enzyme G9a acts like a traffic jam, reducing the ability of cancer fighting immune cells to reach the tumour,” Mr Kelly said.

“Building on the group’s previous work, we explored how targeting the G9a enzyme could help in the fight against melanoma. Our lab experiments showed inhibiting the G9a enzyme led to higher levels of LC3B proteins so the immune system could re-engage in the fight against melanoma both on its own, and in combination with immunotherapy.”

Associate Professor Lee said the findings provided hope of new treatment options in the future.

“We are now also working to develop a drug that can effectively inhibit the G9a enzyme,” Associate Professor Lee said.

“We believe blocking the activity of G9a enzymes will in turn raise the level of LC3B protein, making patients more responsive to immunotherapy and possibly even other treatments.

“We are actively working to develop a drug that can be used to treat patients, but this will take time.”

Associate Professor Lee said the researchers plan to expand the study using a larger set of patient samples to test the robustness of the prototype test to predict immunotherapy resistance.

This article originally appeared on the QIMR Berghofer website .

WEHI researchers have identified a key molecular regulator involved in the progression and spread of stomach cancer, suggesting a potential new approach to treat this devastating disease.

The team discovered that removing the inflammatory signalling protein TNF in a laboratory model prevented early-stage stomach cancers from progressing to a more severe stage that, in humans, is much harder to treat. This discovery suggests that stomach cancers may respond to medicines that inhibit TNF. Of note, drugs that inhibit TNF have already shown success in the clinic for certain other diseases, particularly rheumatoid arthritis.

The research, published in the journal Gastroenterology, was led by Dr Lorraine O’Reilly, Dr Tracy Putoczki, Professor Andreas Strasser, Dr Jun Ting Low and Dr Michael Christie, who is also a clinical pathologist at The Royal Melbourne Hospital.

At a glance

• Stomach cancer is often diagnosed at advanced, hard-to-treat stages – and better treatments are urgently needed.
• Using a laboratory model, our researchers revealed that the inflammatory signalling protein TNF is required for stomach cancer to develop and progress to an advanced, invasive stage.
• This discovery suggests that medicines that inhibit TNF – which are already in clinical use for other diseases – may be an effective new treatment for stomach cancer.

Pinpointing the culprits

More than one million people around the world – including more than 2000 Australians – are diagnosed with stomach cancer each year. This cancer is often detected late, at hard-to-treat stages, with fewer than one-third of Australians with stomach cancer surviving for five years after their diagnosis.

Understanding which factors are important for stomach cancer to develop and progress to invasive stages could lead to much-needed better treatments. To do this, the research team used a laboratory model of stomach cancer that they had developed, Dr O’Reilly said.

“Human stomach cancer can be caused by prolonged inflammation and our model of stomach cancer, that is driven by the absence of the protein NF-KB1, accurately reflects the sequential changes seen in human stomach cancer as it progresses from an early, inflammatory stage.

“We discovered that invasive stomach cancers contain high levels of various factors involved in inflammation, including four soluble proteins called cytokines.

“By removing each of the four cytokines that were elevated in our model, we could assess how important each one was. This revealed that the cytokine TNF was required for the progression of stomach cancer,” she said.

Potential new therapies

The discovery that TNF is a critical driver of stomach cancer development raised the possibility of this cytokine being a potential therapeutic target, Dr Putoczki said.

“Many therapies have shown great promise in treating inflammatory diseases by targeting specific cytokines,” she said. “Excitingly, there are already medicines in clinical use that block TNF, most notably for the treatment of rheumatoid arthritis.

“Our research suggests these therapies could be an effective and safe way to prevent the progression of stomach cancer to more severe, invasive forms. This is an area we are looking at in more detail.”

This article originally appeared on the WEHI website. ACRF has given WEHI $9 Million for four cutting-edge cancer research.

The ACRF INCITe Centre will enable researchers to see immune cells and molecules move and interact below the surface of tumours and deep inside tissues.

A $3M grant from the Australian Cancer Research Foundation will establish a custom-built microscopy centre to image the ‘dark space’ of cancer-immune interactions, which will enable new advances in cancer research.

Based at Sydney’s Garvan Institute of Medical Research, the ACRF Centre for Intravital Imaging of Niches for Cancer Immune Therapy (ACRF INCITe Centre) will house two Australian-designed microscopes. This will enable researchers to see immune cells and molecules at the cancer site move and interact in real time – below the surface of tumours and deep inside tissues.

The ACRF INCITe Centre will address a major challenge in the treatment of cancer: why some patients respond to immunotherapies, designed to arm the immune system against cancer, while others do not.

“Cancers hide from the immune system in highly complex and dynamic environments that can’t be visualised by conventional microscopes,” says Chief Investigator Professor Tri Phan from the Garvan Institute. “The custom-built microscopes in the ACRF INCITe Centre will overcome the current limitations and allow us to finally answer questions that we have not been able to address before. Our goal is to make a promising cancer therapy even more effective for patients.”

“Never in ACRF’s history has backing bold ideas for cancer research been more crucial. We are proud to announce funding of this world-leading Australian research centre today to enable new discoveries that will lead to better patient outcomes,” says ACRF’s CEO Kerry Strydom.

Bridging a gap in immunotherapy

Immunotherapy has greatly advanced cancer treatment over the past four decades and is highly effective for some cancer patients, including for half of those with advanced melanoma.

However, immunotherapy is effective in less than 30% of patients with advanced lymphoma, kidney, bladder and lung cancer, and for those affected by breast, prostate and pancreatic cancer, the treatment is rarely effective.

“For immunotherapy to be more effective, we need to bridge the gap in our understanding of how cancer cells interact with their local microenvironment to adapt to constantly changing conditions and how they evade immune destruction. These interactions are often short-lived and occur in sites that are inaccessible to visualisation by conventional microscopic techniques,” says Chief Investigator Associate Professor Marina Pajic, from the Garvan Institute.

Imaging beyond current limits

The ACRF INCITe Centre will enable researchers to see inside tumours at unprecedented temporal and spatial resolutions. “This is the first intravital imaging centre dedicated to studying cancer–immune cell interactions in vivo and at the molecular level. It will give us a comprehensive view of how the immune system can work to fight cancer,” says Chief Investigator Professor Paul Timpson, from the Garvan Institute.

Two custom microscopes housed at the INCITe Centre – the ‘EndoNICHEscope’ and ‘Molecular NICHEscope’ – will enable researchers to study living tumours inside mouse models, in real time.

The EndoNICHEscope will allow researchers to identify cancer and immune cells in previously inaccessible regions of tumours, using cutting-edge two-photon excitation imaging techniques, innovative adaptive optics technology and a minimally invasive microendoscope developed at the Australian National University by Chief Investigator Dr Steve Lee. The Molecular NICHEscope will image dynamic cancer-immune cell interactions and signalling events in unprecedented detail, in otherwise inaccessible organs such as the lung and pancreas, using a state-of-the-art FLIM detection unit and sophisticated image processing software.

World-leading collaboration

The INCITe Centre, scheduled to launch next year, unites an interdisciplinary team of world-class experts in cancer biology, physics and engineering at the Garvan Institute, the Australian National University, University of Technology Sydney, QIMR Berghofer, Harry Perkins Institute of Medical Research, the Centre for Cancer Biology and Olivia Newton-John Cancer Research Institute.

Collaborators from 23 research labs from across Australia will access the technology via a virtual network to investigate fundamental cancer biology, the role of cells, molecules and genes that regulate cancer-immune interactions, and new therapeutic approaches to enhance immunity against cancer.

The researchers will address crucial questions, such as how immune cells can be activated in a breast cancer, how cancer-immune interactions can be manipulated to target cancer cells lying dormant in niches of bones, and how cancer cells use ‘immune cloaking’ to stay undetected. 

“The vision of the Centre is to implement radical new imaging technologies to investigate and manipulate the cancer–immune cell interactions. Thanks to our extensive clinical connections, we plan to progress any new discoveries to clinical trials as quickly as possible,” says Professor Phan.

This article originally appeared on the Garvan Institute website. Garvan Institute was a recipient of one of our 2020 grants – read more about the $6 million of innovative funding awarded thanks to our supporters here.

Despite the challenges of 2020, we wanted to ensure that we could still all come together and celebrate the science and the work that’s been made possible thanks to our donors’ generosity. This year, our celebration was a virtual one, called Behind the Science.

Behind The Science showcased the projects awarded ACRF funding in 2020 and was hosted by comedian and mathematician Adam Spencer. Adam’s entertaining and understandable interviews with the amazing grant recipients unveiled their innovative ideas and explored the potential impact that these projects will have in advancing to a world without cancer. 

You can watch a recording from the evening below:

In 2014, our incredible supporters’ generosity allowed us to award $2.5 million to Walter and Eliza Hall Institute. The grant established the ACRF Breakthrough Technologies Laboratory, to analyse genetic mutations at the individual cell-level.

One of the technologies supported was CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat), which was awarded the 2020 Nobel Prize for Chemistry.

Highlights of Progress

In 2019, the ACRF Breakthrough Technologies Laboratory was integral to aspects of around 55 published investigations related to various types of cancers. 

Every year since 2015 approximately 67 staff and 10 students have used, accessed, or been involved in projects within the ACRF Breakthrough Technologies Laboratory.

The most significant finding so far has been the development of new chemotherapy combination strategies to target 413 genes potentially linked to colorectal cancer.

Research progress in 2019

Currently, there are two screens that are in development which will be run in parallel using the arrayed mouse whole genome CRISPR library. The first screen has been designed to identify genes that control neutrophil nuclear morphology. 

Neutrophils are the first leukocyte responders of the innate immune system, and have unique migratory and functional capabilities are largely impacted by their nuclear shape, composition and plasticity. A well defined, inducible model of neutrophil maturation will be used with high content confocal microscopy (Opera Phenix™) as the endpoint readout. 

The second screen in development is a synthetic lethal screen to identify targets that either sensitise cells or confer resistance to inhibition of the pro-survival protein MCL-1. Several potent and selective MCL-1 inhibitors are now in the clinic for the treatment of hematological malignancies and this study aims to help define improved strategies for cancer therapy. The screen design utilises the Intellicyt® iQue Screener PLUS, a high throughout, automated flow cytometer which enables analysis of suspension cell lines.

The Janus liquid handling platform continues to be used extensively to support multiple projects at WEHI. These include follow up studies from one of the first functional genomic screens performed to identify synthetic lethal combinations with standard of care therapeutics in colorectal cancer.

These studies have now been extended to include testing of patient-derived organoids. Following our discovery of BCL2 mutations as a cause of resistance to venetoclax in patients with chronic lymphcytic leukemia, we have been able to further explore resistance to Venetoclax using facilities within the ACRF Breakthrough Technologies Lab.

We have used mass cytometry (CyTOF) to make new discoveries in the mechanisms of resistance employed by blood cancers to resist treatment with targeted therapies. The in-kind support from WEHI established key reagents and analytical platforms for us to perform these experiments.

Multiple myeloma is the second most common blood cancer. Although most treatments can be effective, these almost always fail as the cancer changes to become resistant. We developed a new CyTOF approach to analyse the configuration of cell death proteins in millions of individual myeloma cells after they are exposed to cytotoxic treatments. This allowed us to visualise the “decision-making” process in these cells. We employed machine learning approaches to determine the most critical changes in predicting whether the cells live or die. We then tested these predictions using a new inhibitor of the survival protein, MCL-1, and found that it synergised potently to kill more myeloma cells than standard-of-care therapies. Indeed, myeloma cells taken directly from patients also responded better to this combination. These findings were recently published.

We have since developed our CyTOF platform for the analysis of patient samples in clinical trials. We know this approach has been effective in discovering resistance mechanisms in other blood cell cancers and are excited to apply them to multiple myeloma.

Our capacity in CyTOF analysis has also been applied to profiling immune cells in lung cancer specimens from patients. In unpublished work, we have made new insights into the types of immune cells implicated in frustrating the immune response to cancer. We are preparing these for publication and believe they will inform new treatment options to control metastasis.

In 2016, thanks to the generosity of our dedicated supporters, The Institute for Molecular Bioscience located in Queensland was awarded a grant for $2.3 Million to establish the ARCF Cancer Ultrastructure and Function Facility (ACRF CUFF).

We are pleased to share with you a research update from the facility, to share the incredible cancer research that has taken place since this grant was awarded. 

The ACRF CUFF contains complementary state-of-the-art equipment for examining the 3D ultrastructure of cancer cells, using the newest microscopes and high-performance computing for laser imaging of live cells. 

Throughout 2019, a growing number of users from UQ and from other universities, hospitals and institutes around Australia made use of ACRF CUFF for biomedical research aimed at understanding cancer biology, developing drugs and establishing new models for cancer research. 

Impact Amplified

Importantly, ACRF CUFF continues to leverage further funding and support for cancer research. 

New cancer research groups and talented new group leaders have been recruited to IMB, attracted by the state-of-the-art equipment in ACRF CUFF. 

New capabilities for cancer research are created by using ACRF CUFF for training courses and promotion of the latest microscopy technologies and a highlight of the year saw ACRF CUFF hosting events and courses for microscopy professionals and researchers from throughout Australia. 

A substantial amount of competitive grant and fellowship funding was awarded in 2019 to groups using ACRF CUFF. 

The facility seeks to expand public interest and support for cancer research by hosting tours and public events. 

Finally, further expansion of the ACRF CUFF facility itself was made possible by additional internal and external equipment funding as the facility continues to keep abreast of the latest technological and scientific developments. 

This facility – a much-acclaimed legacy of the generosity of ACRF supporters – continues to be a source of exciting capacity for discovery and development in cancer research, supporting the work of a growing number of dedicated researchers, clinicians and trainees. The research outputs from ACRF CUFF are enthusiastically tracked by scientists, clinicians and the public through the scientific literature, conferences and social media. 

Thanks to the generosity of our supporters, the ACRF Centre for Imaging the Tumour Environment was officially opened on 4 October 2019 and is used by researchers of the Olivia Newton-John Cancer Research Institute (ONJCRI) and La Trobe Institute of Molecular Science (LIMS) to examine how cancer cells interact with neighbouring populations to create micro-environments supportive of tumour development. 

Insights into enhancing our ability to disrupt and treat these interactions are provided by imaging machines including Multiphoton and Confocal Microscopes, and a NanoString Molecular Barcoding Scanner. 

Since the first piece of instrument was commissioned in late September 2018, more than 40 individual researchers from five Melbourne Research Institutions have utilised the equipment and research support provided by the Facility at the Olivia Newton-John Cancer Research Institute. 

Over the course of this reporting period, the ACRF Centre for Imaging the Tumour Environment has commissioned the first Next Generation Zeiss Multiphoton microscope in Australia, as well as the Next Generation Zeiss Inverted Confocal platforms, cementing the Facility as a world-wide state-of-the-art imaging centre for our research teams. This research is only possible thanks to people like yourself, who have generously given to help outsmart cancer.

Vision for ACRF Centre for Imaging the Tumour Environment: 

1. To enable cancer researchers and clinicians at the ONJCRI and its partners at the La Trobe Institute for Molecular Science (LIMS) and the immediate Austin Health precinct to perform cutting edge characterisation of interactions between tumour cells and the tumour microenvironment. 
2. To exploit with advanced microscopy one of Australia’s largest existing portfolios of novel therapeutic reagents targeting the tumour microenvironment. 

Projects undertaken within the ACRF Centre: 

The following cancer research teams and Institutes are using the ACRF Centre for Imaging the Tumour Environment. 

• Cancer and Inflammation Laboratory, ONJCRI (gastric cancer) 

• Cancer Immuno-Biology Laboratory, ONJCRI (melanoma) 

• Matrix Microenvironment & Metastasis Laboratory, ONJCRI (breast cancer) 

• Metastasis Research Laboratory, ONJCRI (breast cancer) 

• Oncogenic Transcription Laboratory, ONJCRI (colorectal cancer) 

• Receptor Biology Laboratory, ONJCRI (prostate and colorectal cancer) 

• Tumour Progression and Heterogeneity Lab, ONJCRI (breast cancer) 

• Tumour Targeting Laboratory, ONJCRI (brain, breast, colorectal cancer) 

• Humbert Laboratory, La Trobe University (breast cancer) 

• Hannan Laboratory, Mercy Hospital for Women (pre-eclampsia) 

• Lewin and Cameron Laboratory, Peter Doherty Institute for Infection and Immunity (HIV anti-retrovirus resistance) 

• University of Melbourne Department of Surgery (liver cancer) 

An innovative technique to improve cancer treatments using tumour biopsies less than 30 minutes after they’re taken has been developed at The University of Queensland.  

The ‘Drug uptake in ex Vivo tumours’ technique was developed after researchers found fresh patient tumour biopsies responded differently to treatments than the tissue cultures traditionally used.

Its inventor, UQ Diamantina Institute’s Dr Fiona Simpson, said it could be used to show how long antibodies stayed active in patients, or when antibodies were taken into the tumour where they’re destroyed.

“The technique will significantly help pharmaceutical and technology companies design future cancer drugs,” Dr Simpson said.

“Until now, scientists have only looked at how cancer drugs interact with tissue culture, not fresh tumours.

“Applying medications to tissue culture doesn’t always work because the immune system responds differently in a body.

“I thought it was pretty obvious that we should test cancer drugs on actual tumours, but people kept telling my research team that it wouldn’t work!”

The technique includes a step-by-step process to help drug companies and researchers better understand how drugs interact with patients, and respond to targeted treatments.

“We’ve created a comprehensive process, including detailed videos on tumour extraction and drug-testing processes, for researchers around the world to use,” she said.

“The technique is useful for all types of cancers, and we’re very excited about its possibilities.”

The research was published in Cell Press’ STAR Protocols.

This article originally appeared on the University of Queensland Diamantina Institute website. ACRF has granted $16.1 million to the Diamantina Institute for cutting-edge cancer research.

In 2015, thanks to the generosity of people like yourself, ACRF awarded $2 million to the Australian Synchrotron for the creation of the ACRF Detector.

The ACRF Detector would enable the shape and function of proteins to be analysed on the Australian Synchrotron’s Micro Crystallography (MX2) beamline, in a fraction of the time taken. This would mean a ten-fold increase in capacity, crucial to accelerating cancer drug development.

The brilliant light of the MX2 beamline allows researchers to investigate the arrangement and activity of molecules in cancer cells (and cancer treatments) at a level of detail that is not possible at any other Australian research facility. Your support has enabled not only more research to take place, but the production of data of greater accuracy and quality. 

This means researchers will gain answers much faster, shortening the time from laboratory research to clinical trial, which tests the performance of new cancer drugs. In the last year, the Detector has been revolutionary for the MX2 Beamline at the Australian Synchrotron.

ACRF assess each grant we give based on anticipated future impact of the projects, to ensure every dollar donated generously by people like you makes the biggest difference possible to cancer research. 

We use four categories to do this. These include the human impact – the direct health benefits to people with cancer, the societal impact – the benefits to carers, family members and broader society, the intellectual impact – or the new knowledge, outcomes, jobs and research, and the leverage impact – or how the institute can snowball further funds from our initial investment. 

We are so pleased to see this project excel in each of these impact categories, and go even further. Recently, a team of Monash University researchers have used the facility to determine the 3D-structure of a SARS-CoV-2 protein at atomic resolution. These structures could potentially be used in drug screening and in targeted experiments to disrupt the replication of the COVID-19 Virus.

The COVID-19 pandemic has called for unprecedented research to be conducted into viruses. Although the focus of the research we fund will always be cancer, we’re proud that the contribution of our community will help save more lives during this pandemic. 

Together we can outsmart cancer, because of talented researchers such as these, and people like you. Thank you for entrusting us with your donations, and helping to make impact on the lives of people affected by cancer every day. 

New QIMR Berghofer research has identified how an early genetic change in blood and bone marrow cells paves the way for the development of some blood cancers.

The research has placed a new target on treatment of myelodysplastic syndrome and acute myeloid leukaemia.

The discovery provides a new target for treatment of the blood cancers myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). MDS is often a precursor cancer to AML, a highly aggressive form of leukaemia.

The research findings have been published in the prestigious international journal Nature Communications.

Lead researcher and the head of QIMR Berghofer Medical Research Institute’s Cancer Program, Associate Professor Steven Lane, said his team engineered the transcription factor Cdx2 into normal mouse blood cells, and this resulted in the development of MDS and AML.

“We found that Cdx2 hijacks and corrupts how other genes behave in blood and bone marrow cells. It sows the seeds of vulnerability which then allows the development of other genetic mutations that lead to cancer,” Professor Lane said.

“It’s a step-wise process that closely reflects the progression of human MDS to AML, where genetic mutations occur in blood and bone marrow stem cells and these immature cells become a reservoir for leukaemia.

“Cdx2 isn’t usually present in normal blood formation, so our study on mice showed its presence in the early stem cell stage of development was the likely driver of leukaemia.

“It’s possible that targeting the early processes leading to MDS in patients might prevent the acquisition of other mutations that lead to acute leukaemia.”

Additional study on the effects of an anti-leukaemia drug on the Cdx2 gene 

As part of the study the researchers also tested how existing anti-leukaemia drug azacitidine affected the Cdx2 gene.

Associate Professor Lane, who is also a clinical haematologist at the Royal Brisbane and Women’s Hospital, said azacitidine is currently funded under the Pharmaceutical Benefits Scheme for the treatment of MDS.

“We found that reducing the dosage of the medication and giving it over a longer period of time was more effective in killing off Cdx2 cells and leukaemia cells than the standard treatment regimen that provides high dosages of azacitidine at intermittent intervals,” he said.

“There is a new, oral form of azacitidine that might be more suited to the lower dose, extended treatment regimen, but further tests will be necessary to determine its efficacy in patients.”

According to the Leukaemia Foundation, MDS is a common blood cancer in patients over the age of 60. It can affect children but is less common in younger age groups. It can turn into AML, which is a rare type of leukaemia, accounting for 0.8 per cent of diagnosed cancers, and is hard to treat.

The study findings can be accessed on the Nature Communications website.

The research was funded by the National Health and Medical Research Fund of Australia and the Leukaemia Foundation of Australia. Celgene – a Bristol-Myers Squibb company supplied azacitidine and provided additional research funding for the study.

Quick Facts about MDS and AML:

MDS affects between 20 and 50 people per 100,000 according to the Leukaemia Foundation. It develops slowly and patients often do not show symptoms for a long time.

About 900 Australians are diagnosed with AML each year. It can occur at any age but is more common in adults over the age of 60. About 50 children (0-14 years) are diagnosed with AML in Australia each year.

Fewer than one in four people are still alive five years after being diagnosed with AML according to Cancer Australia.

This article originally appeared on the QIMR Berghofer website. ACRF has given three grants to QIMR Berghofer totalling over $7 million for world-class cancer research.

THE GRANT

In 2015 ACRF awarded $2 million to The Australian Synchrotron. The ACRF Detector funded would enable the shape and function of proteins to be analysed on the Australian Synchrotron’s Micro Crystallography (MX2) beamline in a fraction of the time taken, providing a ten-fold increase in capacity crucial to accelerating cancer drug development.

The capital investment was used  to significantly expand the capability of the Australian Synchrotron Micro Crystallography (MX2) beamline. This technology accurately analyses the 3D shape and functional interaction of proteins. 

The brilliant light of the MX2 beamline allows researchers to investigate the arrangement and activity of molecules in cancer cells (and cancer treatments) at a level of detail that is not possible at any other Australian research facility. 

By introducing the capacity to process large numbers of micron sized protein crystals, the ACRF Detector increases capacity of this crucial beamline, enabling many more research studies to take place, while producing data of greater accuracy and quality. 

This means researchers will gain answers much faster, shortening the time from laboratory research to the clinical trial, which tests the performance of new cancer drugs. 

The grant was awarded to an esteemed research consortium comprising of micro-crystallography experts from six research institutions across Australia. The ACRF Synchrotron became operational in 2016. 

At the time the ACRF investment in this key cancer research technology, was available at only a handful of other synchrotron facilities around the world.

Dr Rachel Williamson with the ACRF detector on the MX2 beamline.

PROGRESS in 2019

The ARCF Eiger 16M Detector has been revolutionary for the MX2 Beamline at the Australian Synchrotron. From an operational perspective, 2019 saw the detector collect 51,064,846 diffraction images, associated with 71,460 datasets across 240 distinct group experiments. Approximately 5 petabytes of raw (uncompressed) data were generated by the ACRF detector in 2019 prior to reduction, processing and analysis.

Use of the ACRF Detector on the Micro-Crystallography (MX2) beamline has continued to grow, and the Macromolecular Crystallography beamlines at the Australian Synchrotron (MX1 and MX2) produced a record number of publications in 2019. More than 210 peer-reviewed scientific journal articles were published in the highest quality journals such as Science, Nature Immunology, Nature Cell Biology, Trends in Biochemical Sciences and Science Translational Medicine.

Large numbers of protein structures from the Australian Synchrotron (~290) were also deposited in the worldwide Protein Data Bank (PDB). Scientific outputs from the MX2 beamline and the ACRF Detector have increased compared to 2018, with 89 PDB structures and 60 journal publications based on data acquired using the ACRF Detector.

In 2019 one of the applicants for the grant for the ACRF Detector (Peter Czabotar from the Walter and Eliza Hall Institute for Medical Research) received the Prime Minister’s Prize for Innovation. Dr Czabotar has also been a productive user of the ACRF Detector during the year, with a publication resulting from use of the detector appearing in the journal Nature Communications.

The Australian Synchrotron has continued to deliver excellent science outputs and outcomes in 2019. This is evidenced by a record number of 608 peer-reviewed journal publications resulting from research undertaken at the facility. Over 1/3 of these publications (214) resulted from structures determined using the MX1 and MX2 beamlines, demonstrating the importance of these beamlines to the scientific program at the Australian Synchrotron. The number of journal articles published in 2019 that contain data taken using the ACRF Detector continues to increase in line with expectations based on the lead-time between data collection and publication. Starting with 4 publications in 2017, there were 311 in 2018 and more than 60 in 2019. Over the next few years we will see continued growth to the point where almost all MX2 publications (which account for the majority of publications on MX1 and MX2) will result from data collected using the ACRF Detector. 

2019 saw at-least 88 research theses published containing results from Australian Synchrotron beamlines; the vast majority being for Doctoral Theses. This is a substantial underestimate of the actual total number of research theses, which usually numbers more than 150 per annum. More than 1/3 of these research theses contain data from the MX1 and/or the MX2 beamlines. The Australian Synchrotron StephenWilkinsThesisMedalfor the most outstanding doctoral thesis in 2019 was awarded to Dr Angus Cowan (WEHI) for his thesis: Structural Investigations of Pro-apoptotic Bcl-2 Family Proteins. This research was centrally focused on understanding key biomolecular mechanisms associated with cancer and cell death, with his work also contributing to the development of the drug Venetoclax.

Read the full report here

In 2018, ACRF granted $2 million to Griffith University to establish the ACRF Centre for Compound Management and Logistics at Compounds Australia – Australia’s only dedicated compound management facility. Below is an update on the important work that has been done since that time.

“Our greatest challenge today is COVID-19 and the impact on the global economy. Our greatest success is the ability to adapt and deal with the problems that arise along the way. Compounds Australia is housed at the Griffith Institute for Drug Discovery (GRIDD), a biomedical research institute dedicated to developing innovative new solutions for devastating conditions including cancers, infectious diseases (e.g. malaria, drug resistance), neurological disorders (e.g. Parkinsons disease) and spinal cord injury repair. 

Compounds Australia’s new equipment platform

GRIDD’s Compounds Australia is Australia’s only integrated compound management facility. This highly specialised facility maintains and manages a library of compounds and natural products and makes these available at low cost to academic and not-for-profit researchers. Demand for these services continues to increase every year, however, the current equipment is approaching end of life. In response, management has embarked upon an exciting project to purchase and install leading-edge and cost-effective equipment. This installation will be the first time in the world that this technology has been implemented in an academic environment

The installation includes much greater storage coupled with robotic systems and software that together will significantly increase capacity and allow for continued expansion in workload and customers while keeping manual involvement manageable.

Steering Group Established

With the project undergoing significant growth, we are pleased to announce the Steering Group has been established, chaired by Professor Katherine Andrews. The role of the Steering Group is to provide advice, ensure delivery of the project outputs and ensure the achievement of project outcomes. Wilma James, Compounds Australia Strategic Business Manager, and Moana Simpson, Compounds Australia Facility Manager, provide the technical, operational and project input to support the Steering Group through the project phases.

Brooks Equipment Installation

The Brooks equipment, in all its disassembled parts, arrived on Thursday 5th March in a 40ft shipping container!  The Brooks “Build” team of three were inducted and ready to work from the 9th March, ahead of schedule.  The SampleStoreII was built from the ground up within the main Compounds Australia laboratory, with an integrated Plate Selector and acoustic technology (AcoustiX) tube picker, the central robot arm will be able to manoeuvre the combined 4,000 microplate and 400,000 AcoustiX tube capacity of the store.  Additionally, Compounds Australia has an integrated handoff to enable full integration to the new HighRes Biosolutions robot platform and a manual input/output module for offline processing.  The build was completed in a record nine days and testament to the hard – working team from Brooks.

The next phase of the process will have the store commissioned, with Facility Manager, Moana Simpson, and Assistant Manager, Rebecca Lang, putting it through its paces during site acceptance testing, following by the remaining staff receiving training. This will be the first worldwide installation and commissioning of the AcoustiX microtube in an Academic environment and the team at Compounds Australia is working with the Brooks team to have this online following COVID-19 disruptions.”

This article originally appeared in the Compounds Australia Newsletter.

Activating two different types of immune cells at the same time has been shown to boost the effects of immunotherapy to find and kill cancer cells in solid tumours according to researchers from Peter Mac.

Adoptive T cell therapies, including chimeric antigen receptor (CAR) T cell therapy, which use genetically engineered killer immune T cells, are emerging forms of immunotherapy that redirect the immune system to target cancer.

This treatment approach can allow treatments to be tailored to each individual, and has been used very successfully to treat certain blood cancers, such as some types of leukaemia.

However, CAR T cell therapy has had limited success in solid tumours such as those of the breast and lung.

Researchers have now found a way to add a new tool to the immunotherapy arsenal, by boosting the activity of immune cells called dendritic cells (DCs) to aid in the recognition and attack of cancer cells.

This new approach, developed by researchers at the Peter MacCallum Cancer Centre, led by Dr Junyun Lai, Dr Sherly Mardiana, Prof Phillip Darcy and Dr Paul Beavis, can overcome many of the issues with conventional immunotherapy.

“One of the major impediments to effective T cell therapy is that in many cases not all cancer cells within a single tumour look the same. In fact, it is common to have high variability of the target protein recognised by the CAR T cells inside the same tumour, an effect known as heterogeneity,” explains senior author on the study Dr Paul Beavis.

“Engineered CAR T cells are very effective at killing the cancer cells that express the target protein. But, unfortunately they are not very good at finding cancer cells that lack this target protein.”

The key to overcoming this issue, Dr Beavis says, could be to recruit and boost other immune cells, including DCs, to lend the T cells a hand.

“Activating the DC immune cells could overcome cancer cell heterogeneity, as DCs are specialised in activating the body’s own immune system. By boosting immune DCs, these DCs are then able to orchestrate a new immune response against the cancer,” says Dr Beavis.

To test this, study co-leads Dr Lai and Dr Mardiana engineered in the laboratory specialised T cells capable of producing a powerful molecule that can expand DCs at the tumour site.

“When we placed these engineered T cells into mice with tumours we found they were able to trigger an influx of DCs into tumours. When we combined the engineered T cells with drugs that further activate immune cells, we found that we could shrink tumours far more effectively,” says Dr Lai.

“What was really exciting about this approach is that we were able to stimulate the body’s immune system to attack multiple targets on cancer cells, helping to overcome the issue of heterogeneity.”

Prof Darcy, co-senior lead on the research, says that this is an important advancement in overcoming tumour heterogeneity that could lead to immunotherapies that are far more effective in the future.

“Our data suggest that augmenting DCs is a promising strategy to overcome the clinical problem of tumour cell escape due to lack of immune cell recognition following adoptive cell therapy,” say Prof Darcy.

“This is an exciting time for cancer immunotherapy. Our research shines a light on DCs as an important new component in the next generation of immune-targeting therapies for the treatment of solid cancers,” says Dr Beavis.

The paper, entitled Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity was published in the journal Nature Immunology.

This article originally appeared on the Peter Mac website. ACRF has given $9 Million to Peter Mac for research into all types of cancer.

In 2014, thanks to the generosity of our donors, ACRF awarded $2.5 million to support three unique cancer imaging and targeted radiotherapy devices through the development of the ACRF Image X Institute.

These include an MRI-Linac, a real-time cancer imaging and targeted therapy system; the Nano-X, a smarter, smaller cancer radiotherapy system and a robotic imaging machine to advance patient connected imaging. 

About ACRF Image X Institute

The ACRF Image X Institute, based in Sydney, is a world-leading research centre for basic and translational medical innovation. The work focuses on radiation oncology imaging and targeted radiotherapy systems.

The institute’s purpose is to create, share and apply scientific knowledge to improve health by building new technology for cancer imaging and targeted radiation therapy by:

• Inventing and exploring new ideas that lead to scientific discoveries.
• Applying key discoveries for real-world benefit through first-in-human clinical trials.
• Translating successful clinical trial outcomes into widespread clinical practice to improve global health.

2019 Outcomes

In 2019, key outcomes reported by the ACRF Image X Institute include:

• Clinical studies – 8 studies have been completed; 8 studies are currently recruiting subjects & 9 studies are under development.  A total of 14 sites are involved in Australia and NZ.
• 24 Scientific publications 
• Intellectual Property: 9 Patents filed with 13 license agreements.

Two articles were published by the popular science Physics World:

The first article was based around the question: how can we reduce the size, reliability and the room and equipment cost of radiotherapy? The answer is to gently rotate the patient rather than a 3-tonne complex and sensitive radiation source. This idea has led to the development of the Nano-X cancer radiotherapy system in partnership with the Prince of Wales Hospital. Dr Paul Liu, who is leading the development and research program for the Nano-X, was interviewed about this project.

In addition, Tess Reynolds’ Best in Physics work on her patient connected imaging project ‘ACROBEAT’ was highlighted by Physics World.

Leading through Unique Capabilities

ARTIS pheno training and installation of real-time control

The ARTIS pheno C-Arm is an advanced robotic imaging system, purchased with funding from the ACRF grant, and situated in the Hybrid Theatre of Sydney Imaging. Through a research agreement with Siemens Healthineers Image X is the only research group provided with real-time control of the operation of this imaging system. Two scientists from Siemens Healthineers in Germany visited to install the control addition and provide training. This installation will allow the experimental validation of methods developed by A/Prof Ricky O’Brien and Dr Tess Reynolds to adapt image acquisition to the patients’ cardiac and respiratory signals.

Outcomes enabled by ACRF Supporters

“I would especially like to thank the ACRF for its funding and support going forward, which is instrumental in enabling us to carry out our ground-breaking research and ensures we can work towards better outcomes for cancer patients.” says Paul Keall, Ph.D, a Professor and NHMRC Senior Principal Research Fellow Director at the ACRF Image X Institute

International Recognition

Professor Keall continues with a note of congratulations for his team.

“In 2019 we were able to congratulate two of our Higher Degree Research students on their awards. Ben Cooper whose PhD thesis is entitled, ‘The investigation of novel x-ray imaging technique in radiation oncology’.
It was fantastic that Dr Ben Cooper won the 2019 Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) Better Healthcare Technology Foundation PhD award for his PhD thesis. Ben’s award in 2019 follows Brendan Whelan’s award in 2018 and Sean Pollock’s in 2017.”

“Ben did his PhD part-time, whilst working full time – he is now Chief Physicist at Canberra Hospital. I am also very proud of Fiona Hegi-Johnson who also graduated in 2019. Fiona Hegi-Johnson whose PhD thesis ‘Let there be light: Harnessing the Power of New Imaging Technologies to Improve Outcomes for Lung Cancer Radiotherapy Patients’, has subsequently obtained a Peter MacCallum Cancer Centre Clinician Researcher Fellowship, a wonderful recognition of Fiona’s achievements and will enable her to carry out further research to improve cancer imaging, biology understanding and targeted treatments.”

“Our PhD students are carefully selected on their outstanding capabilities and it is rewarding Nicholas Hindley, a PhD student won a very highly competed and prestigious Fulbright Foreign Student Program and will spend part of next year at Massachusetts General Hospital/Harvard Medical School, in addition to visiting other sites where machine learning and image reconstruction are strong themes.”

“Nicholas was successful in receiving a Cancer Research Network Postgraduate Conference Travel Grant. Nicholas also received the Most Outstanding Presentation Award at the MedPhys19 annual NSW/ACT medical physics conference, along with Natasha Morton who received the Postgraduate Award. It was great that Emily Hewson was selected for a Sydney Vital Scholar Award.”

“It is always gratifying when our staff are recognised and rewarded for their outstanding work and several early career researchers have established their leadership in their fields.”

“Paul Liu was awarded a 3-year Early Career Fellowship for ‘Upright radiotherapy for improved lung cancer treatment outcomes’ David Waddington was also awarded a 3-year early career fellowship ‘Personalising cancer radiation therapy via dynamic MRI-based adaptation to changing tumour anatomy and biology’. Paul and David were two of only four Cancer Institute NSW Early Career Fellowships awarded in 2019.”

“Our work at the Institute has been internationally recognised at the American Association of Physicists in Medicine (AAPM) with three invited talks (Paul Liu and myself), four oral presentations – all from PhD students Emily Hewson (x2), Nicholas Hindley and Natasha Morton, seven snap orals Andy Shieh, Marco Mueller, Paul Liu, Praise Lim, Owen Dillon, Tess Reynolds and Trang Nguyen. In addition, we had three e-posters, Samuel Blake, Kehuan Shi and Elisabeth Steiner.”

These incredible outcomes would not be possible without the generosity of our dedicated supporters. Thank you for enabling this incredible research to take place.

Read the full report

A team of Monash researchers have determined the 3D-structure of a SARS-CoV-2 protein at atomic resolution using the macromolecular crystallography beamlines Australian Synchrotron.

The Nsp9 protein in SARS shares 97 percent of its sequence with its counterpart from COVID-19. The researchers cloned a version of the CoV-19 Nsp9 protein for the experiments.

These structures, which were described in a paper published in the journal bioRxiv, could potentially be used in drug screening and in targeted experiments to disrupt replication of the virus.

Why understanding the protein is vital to the research of a virus

Determining the shape of a protein is a key step in understanding its function and role in replication of the virus.

The Monash researchers also identified a new component of the protein, a macromolecular complex and are in the process of determining how it impacts the function of the protein.  

The COVID 19 virus only produces 27 or so proteins. Scientists across the world are currently trying to understand how to prevent the production of these proteins inside our cells when the virus repurposes our bodies to promote its lifecycle.

Research Fellow Dr Dene Littler, within the laboratory of Prof Jamie Rossjohn from the Biomedicine Discovery Institute, Faculty of Medicine, Monash University, has been examining some of the lesser-understood proteins produced by SARS-CoV-2.

One of these, the non-structural protein 9 (Nsp9) is thought to have a role in RNA binding and the related version of the protein in SARS is known to be important for replication of the viral genome.  

“This will be part of a broad strategy by the world’s scientists to develop entirely new drugs that are specifically targeted at corona viral proteins, blocking the virus’s ability to infect and reproduce in human cells,“ said Littler.

The COVID-19 pandemic has called for unprecedented research to be conducted into viruses

“Viruses such as those that cause the common cold haven’t had sufficient health implications before to warrant large scale drug research programs.

However, in the face of the current pandemic that has obviously changed and we are playing a fast-paced game of catch up”.

“Technological developments such as those made possible by the Australian synchrotron spurred the first forays into rational drug design, in which scientists study the structure and function of molecules in order to work out what drugs might bind to them,” explained Littler.

 In the case of viruses, the intent is to limit their ability to reproduce and allow a patient’s immune system to recover and fight the infection.  

Rossjohn said, “This represents the start of an accelerated program of research within Monash that is aimed at developing new anti-viral treatments as well as understanding how the immune system combats this virus”.

How the MX2 beamline is being used for COVID-19 related research

The Australian Synchrotron fast tracked access to the microfocus crystallography beamline (MX2) for the COVID-19 related research.

Using the new ACRF detector on the MX2 beamline, it took approximately 18 seconds to acquire a data set, which was then used to quickly construct a crystal structure of Nsp9,” said Principal scientist Dr Alan Riboldi-Tunnicliffe.

“MX2 has a powerful narrow beam, which enables us to focus on particular parts of a crystal. The instrument’s ability to capture molecular detail enables you to see how crucial interactions, such as binding. This is important in assessing drug interactions,” said Riboldi-Tunnicliffe.

“One of the reasons the research is so interesting is that it does not focus on the established strategy of targeting a protease. Dene looked at Nsp9 because it has an RNA binding site that has been conserved over its evolutionary history. This means it is less likely to mutate in response to an intervention,” said Principal Scientist Dr Rachel Williamson.

The Australian Synchrotron has kept the MX2 beamline operational in response to the COVID-19 crisis. Researchers are able to send samples to the Synchrotron and use the instrument remotely. 

The Synchrotron has received samples relating to CoVID-19 from Australia, Singapore and China to date.

This article originally appeared on the ANSTO website. ACRF has granted $2 million to Australian Synchrotron for the establishment of The ACRF Detector.

Researchers from the University of Queensland have identified a promising new drug combination that could significantly help the immune system target cancer cells and kill them.

The study published in Cell, describes a treatment that works by combining an intravenous dosage of a well known anti-nausea drug, prochlorperazine (called Stemetil in Australia), with existing cancer treatments. 

University of Queensland scientist Associate Professor Fiona Simpson, who led the exhaustive research project, said it could lead to new treatments for some cancers. 

Dr Simpson has spent the past decade working on the research project, a tribute to her mother who she lost to cancer in 1999.

“The anti-nausea drug works by changing the surface of the tumour cells so that existing cancer drugs which target tumours are better able to interact with the immune system,” Dr Simpson said.

“The result is that cancer cells become sitting targets that can no longer escape the immune system.

“We observed a process we haven’t seen before and which increased the ‘natural killer’ immune cells’ ability to attach to, and kill the cancer. It is almost as if the killer cells become zipped to the tumour cells.”

The treatment can be combined with and improve the effectiveness of existing cancer drugs like cetuximab, trastuzumab and avelumab and was studied on tumours from head and neck, breast and metastatic colorectal cancers in mice, as well as five patients with head and neck cancer.

“These heroic patients volunteered for a ‘no benefit trial’, consenting to have a tumour biopsy followed by a 20-minute intravenous transfusion of Stemetil, and then another biopsy,” Dr Simpson said.

“We were able to show that the Stemetil altered the tumour cell surface in these patients.”

Following the initial findings, the researchers combined Stemetil with an anti-cancer antibody drug resulting in the disappearance of all the tumours from ten mice with head and neck cancer.

Dr Simpson was curious to see what would happen if they re-introduced the same cancer back into the mice four weeks later.

“Amazingly, their cancer was rapidly eliminated – as if the new combination, in addition to being more effective, was also able to teach the immune system how to better recognise cancer cells,” Dr Simpson said.

“The mice developed a long-term immunity to the cancer they initially had.”

The Fiona Simpson Cancer Research group has been working with expert immunologists including UQ’s Dr James Wells to translate the research findings to patient treatments.

“Our long-term vision is to use this approach to not only clear a patient’s cancer in the immediate term, but to prevent their cancer coming back in the future by establishing protective ‘immune memory’,” Dr Wells said.

Dr Simpson’s team is now completing a safety trial of the combination of Stemetil and cetuximab in head and neck cancer, triple-negative breast cancer and adenoid cystic carcinoma patients at the Princess Alexandra Hospital.

The collaboration involved researchers and doctors from UQ’s Diamantina Institute and Institute for Molecular Bioscience, The Princess Alexandra Hospital, Children’s Medical Research Institute, The University of Newcastle and The University of Sydney.

The University of Queensland’s technology transfer company UniQuest will seek to identify commercialisation opportunities.

This article originally appeared on the University of Queensland website. ACRF has provided $17.1 million in funding to University of Queensland’s Diamantina Institute, including a major $9.9 million grant for research into melanoma.

A revolutionary new technology has been applied to reveal the inner workings of individual cancer cells – potentially identifying more effective treatment combinations for people with cancer.

A joint Walter and Eliza Hall Institute and Stanford University team used a technique called mass cytometry (also called CyTOF) to simultaneously analyse the levels of more than 20 different proteins in millions of individual blood cancer cells. This revealed how these cells responded to different anti-cancer medicines, even suggesting potential new treatment combinations.

The research team hope that the new technique could be integrated into clinical trials both to understand why some patients are resistant to anti-cancer therapies, and to predict suitable ‘biomarkers’ for matching patients with the most effective therapies for their disease.

The study was led by Walter and Eliza Hall Institute researchers Dr Charis Teh and Associate Professor Daniel Gray, in collaboration with Professor Garry Nolan and Dr Melissa Ko from Stanford University, US.

At a glance

• A new technique called mass cytometry, or CyTOF, is providing new insights into a range of key proteins in blood cancer cells.
• By studying the blood cancer myeloma, researchers were able to understand why some cells were not killed by standard anti-cancer drugs, and to devise a more effective therapy.
• The team hope to apply their mass cytometry protocol to current clinical trials to better understand why some cancers are resistant to anti-cancer therapies, and to match these patients to other, potentially more effective, treatments. 

Discovering vulnerabilities in myeloma

Cancers are made up of millions of individual cells which are all similar, but not exactly the same. Until recently almost all studies of cancers looked at the cells grouped together, missing any potential differences between individual cells, said Dr Teh.

“We wanted to better understand the molecular differences between individual cancer cells so we could discover how these differences impact the cancer’s response to therapies – for example, whether some cells are more resistant than others to an anti-cancer drug,” Dr Teh said. “We decided that a new technology, called mass cytometry, would be an ideal approach to address this question.”

Mass cytometry can simultaneously measure the quantity of different proteins in a single cell. With funding support from the Australian-American Fulbright Commission, Dr Teh was able to visit Stanford University to learn the technology and develop a test that measures a range of proteins known to regulate cancer cell survival, division, signalling and growth.

“The system we developed simultaneously and precisely measures 26 separate proteins in a blood cancer cell line derived from myeloma – an incurable cancer of immune B cells,” Dr Teh said. “We focussed on understanding why some cells are sensitive to anti-cancer agents, while others are resistant.

“We used machine learning to analyse the mass cytometry results of thousands of cells, and were able to distinguish which cells survived treatment with standard medicines used to treat myeloma – and see how they differed from cells that were sensitive to these medicines,” she said.

The team pinpointed the protein MCL-1 as a key factor determining whether cells lived or died when exposed to the myeloma medicines dexamethasone or bortezomib. MCL-1 is a type of protein that can prevent cell death when overproduced in cancer cells.

“Excitingly, there are already drugs in clinical trials that inhibit MCL-1 – and when we tested these against myeloma cells, we found the MCL-1 inhibitor made the cells more sensitive to dexamethasone. This was even the case in myeloma samples taken from a patient – our system had identified a potential new therapeutic approach for myeloma,” Dr Teh said.

A new approach

Mass cytometry may even have a role in providing real-time detailed analysis of patient samples from clinical trials, Associate Professor Gray said.

“The panel of markers developed in this study gives researchers considerable scope to understand how cancer cells are responding to anti-cancer therapies – and as we found, it can even help to identify better drug combinations,” he said.

“Adding mass cytometry to the analysis of clinical studies could reveal why some patients respond to therapies differently from others, and how resistance to anti-cancer medicines can develop in a small fraction of cancer cells.

“Mass cytometry could also identify a small number of proteins that can be used as specific ‘biomarkers’ that can predict a patient’s response to therapy, and be used to match that patient with the most effective treatments. We’ve already started collaborations with our clinical colleagues to investigate this possibility further,” Associate Professor Gray said.

The research was published in the journal Cell Death & Differentiation.

This article originally appeared on the Walter and Eliza Hall Institute. ACRF has given $9.1 million to WEHI for world class cancer research technology, thanks to the generosity of our donors.

Walter and Eliza Hall Institute researchers have revealed a new vulnerability in lymphomas that are driven by one of the most common cancer-causing changes in cells.

The team revealed that the protein MNT is required for the survival of lymphoma cells that are driven by the protein MYC. Up to 70 per cent of human cancers – including many blood cancers – have high levels of MYC, a protein which forces cells into abnormally rapid growth.

The research, led by Professor Suzanne Cory, Dr Hai Vu Nguyen and Dr Cassandra Vandenberg, suggests that potential therapies targeting MNT could be effective new treatments for MYC-driven cancers.

At a glance

• The majority of human cancers are driven by high levels of the protein MYC, but it has been challenging to develop new medicines that directly inhibit MYC.
• Our researchers revealed that MYC-driven lymphoma cells rely on the protein MNT for their survival, and without MNT the cells rapidly die.
• The results suggest that inhibiting MNT might be an effective new approach for treating MYC-driven cancers.

A new target

High levels of the MYC protein are found in up to 70 per cent of human cancers. MYC controls hundreds of genes, driving rapid cell production, said Professor Cory, who has studied MYC-driven cancers since the early 1980s.

“For many years we hoped for a drug that could directly target MYC as a potential cancer treatment, but to date such inhibitors have been disappointing in the clinic,” she said. “It became clear we needed to look for other vulnerabilities in MYC-driven cancers.”

The team successfully identified a new target for tackling MYC-driven cancers by homing in on the role of a protein related to MYC, called MNT. Their research was published today in the journal Blood.

By deleting the gene encoding MNT from MYC-driven lymphocytes – the type of immune cell from which lymphomas arise – we found that MNT played a significant role in MYC-driven lymphoma development, Dr Vandenberg said.

“In our laboratory models, the incidence of MYC-driven lymphomas was greatly reduced when MNT was absent. This showed us that MNT had a vital role at some stage during lymphoma development,” she said.

“That role became clear when we found that pre-cancerous cells lacking MNT had high levels of apoptotic cell death,” said Dr Nguyen. “Thus, MNT is required to keep MYC-driven cells alive.”

Towards better treatments

Dr Nguyen said that the team went on to examine the impact of depleting MNT from fully malignant MYC-driven lymphomas. “When we did this, we saw that the tumour cells rapidly died,” he said. “This suggests MNT could well be a promising new therapeutic target for MYC-driven lymphomas.”

Professor Cory said the researchers would now look at whether MNT was important in other MYC-driven cancers.

“Inhibiting MNT may also make tumours more susceptible to other drugs such a BH3-mimetics which directly target the cell’s death machinery.

“Although a lot of work remains to be done to develop and test a new MNT-inhibiting therapy, our discovery opens up a new front in tackling MYC-driven cancers,” Professor Cory said.

The research was supported by the Australian National Health and Medical Research Council, the US-based Leukemia and Lymphoma Society, philanthropic support to the Walter and Eliza Hall Institute and the Victoria Government.

This article originally appeared on the WEHI website. ACRF has granted WEHI $5.5 Million for world-class cancer research technology and equipment.

A research team from Harry Perkins Institute of Medical Research that recently invented a drug to stop blood vessels from forming a treatment resistant barrier around some cancers has now discovered the drug can be used to prevent the cancer from spreading.

“We originally developed the drug to overcome a problem in some cancers that grow a chaotic barrier of blood vessels in the tumour which prevents the body’s immune cells and treatments like chemotherapy entering the tumour,” said Professor Ruth Ganss Co-Head of the Cancer and Cell Biology Division at Perth’s Harry Perkins Institute of Medical Research.

“The drug also sets-up lymph-node-like structures within the cancer to draw in a patient’s immune system and greatly enhance a patient’s own capacity to shrink the cancer.

“What we’ve since discovered is that by ‘normalising’ blood vessels the drug also stops cancer spreading because it counteracts the cancer’s influence on blood vessels in other parts of the body.

“Cancer spreads when cancer cells travel through the bloodstream and settle and grow in other organs, like the lung or brain.

“They are able to establish themselves in a distant body part because the primary tumour secretes substances that make blood vessels in other organs ‘leaky’, or easier to penetrate.

“So when cancer cells travel in the blood stream they typically settle and grow where there are optimal conditions that have actually been created by the primary tumour.

“The primary tumour effectively ‘talks’ to the site where the metastasis is going to form so when the floating cancer cells arrive, they find a nice cosy environment in which to grow.

“While this behaviour of cancer was already known, what we have discovered is that we can interfere with this process because of the way this new drug affects blood vessels.

“We’ve discovered it restores the leaky vessels which results in the cancer cells flowing past and not setting up shop.

“For a patient this means that in future it will be possible to remove the primary tumour, then use the new drug to prevent cancer cells in the blood system from successfully attaching themselves to another organ and growing.

“But, if the cancer cells have already settled elsewhere and started growing then the drug can also be used to increase the number of immune cells brought into the new tumour to help it shrink.”

“So we now have a drug that not only opens up the primary tumour for increased immunotherapy and greater treatment access, but it prevents metastatic spreading and if the cancer has already spread, then the drug escalates the patient’s immune response to the new cancer.

“We now know we can interfere early and late in a cancer’s journey,” Professor Ganss said.

Co-author on the publication, Dr Bo He who undertook laboratory work on the drug said the research focused on metastatic cancer because most patients succumb to secondary cancers, not the primary.

“Using the drug that the team developed and published in 2017 in Nature Immunology we explored whether it could prevent metastases as well as improve patient immune response”.

“We’re quite excited that we have moved into a different phase of exploring how this drug could be used.

“So far we’ve successfully applied it to melanoma and lung cancer models in a metastatic setting”, said Dr He.

The research has been published in the internationally renowned scientific journal, Cell Reports and can be viewed at Cell Reports homepage.

This article originally appeared on the Harry Perkins Institute of Medical Research website. ACRF has granted $1.75 Million to fund three pieces of equipment, including a high throughput next-generation DNA sequencer and equipment to isolate single cells from a patient’s tumour.

Perth researchers discover way to enhance immune response and drug treatment of stiff, difficult-to-treat solid cancers.

Some solid tumours are so stiff they make a cracking noise when they are cut by researchers on the laboratory bench.

The fibrous nature of liver, pancreatic and some breast cancers make them difficult to treat. However, five years of research by a team of Perth scientists has resulted in the development of a novel, non-toxic agent that can deliver drugs to the cancer cells embedded in the fibrous matrix.

Research published in EMBO Molecular Medicine showed a non-toxic therapeutic agent boosted immune cells to
selectively remove the fibrous scar tissue allowing cancer treatments to reach their target.

Dr Juliana Hamzah, head of the Targeted Drug Delivery, Imaging and Therapy Laboratory at the Harry Perkins Institute
of Medical Research said by breaking down the fibrous matrix of stiff tumours the patient’s own immune system paved the way for drug treatments to take effect.

“The cancer is like a wound, and a way that our body tries to repair the wound is to grow a scar tissue around it, but that scar tissue makes it very difficult to get to the cancer cells to destroy them.

“It is stiff, non-cellular, has very few blood vessels and impenetrable. The scar tissue is not only a physical barrier but it constricts blood vessels which are key pathways for delivering cancer treatment.

“The barrier around some cancers, such as liver cancer, pancreatic cancer and some breast cancers is like barbed wire.

“We have developed a non-toxic agent that does not affect surrounding healthy tissue.

“The agent activates immune cells to release enzymes that digest the scar tissue. This allows more cancer-killing immune cells to enter the tumour. Our results show that removal of the fibrous tissue dramatically eliminates the drug delivery barrier.

“Tumours treated with the drug we’ve developed are more permeable to anti-tumour immune cells and cancer treatments”, Dr Hamzah said.

The research data have been validated in four laboratories including the Harry Perkins Institute of Medical Research in Perth, the School of Engineering at The University of Western Australia, Sanford Burnham Prebys Medical Discovery Institute, California, USA, and the University California Davis, California, USA.

Dr Hamzah says that now the drug has been proven to have a positive impact on fibrosis, or scar tissue, she is investigating whether it can be used to prevent malignant cancer by treating the early stages of fibrosis in liver cancer.

“If you take liver cancer, it doesn’t start immediately as cancer, it starts as fibrosis, cirrhosis, which then develops into liver cancer.

“Because chronic tissue fibrosis can lead to cancer we aim to investigate whether early treatment with our drug of the pre-cancerous stage, such as liver fibrosis, could prevent development of malignant cancer.

Testing of the drug is due to commence using human tissue biopsies. 

This article originally appeared on the Harry Perkins Institute of Medical Research website. Australian Cancer Research Foundation has granted $5.4 million to Perkins for cutting-edge cancer research infrastructure and equipment.

Drinking coffee does not change a person’s risk of being diagnosed with or dying from cancer, a new QIMR Berghofer study has found.

The research findings have been published in the International Journal of Epidemiology.

Senior author and head of QIMR Berghofer’s Statistical Genetics Group, Associate Professor Stuart MacGregor, said the large Mendelian randomization study looked at data from more than 300,000 people and showed drinking coffee every day neither reduced nor increased a person’s risk of developing any cancer.

“We know that coffee is one of the most popular drinks in the world, and there continue to be mixed messages about the role it plays in disease,” Associate Professor MacGregor said.

“We also know that a preference for coffee is heritable.

“Our two-pronged research looked at whether cancer rates differed among people with different levels of self-reported coffee consumption, and whether the same trend was seen when we replaced self-reported consumption with genetic predisposition towards coffee consumption.

“We found there was no real relationship between how many cups of coffee a person had a day and if they developed any particular cancers.

“The study also ruled out a link between coffee intake and dying from the disease.”

Coffee contains a complex mixture of bioactive ingredients, including substances such as caffeine and kahweol, which have been shown to display anti-tumour effects in animal studies.

Its potential anti-cancer effect on humans has not been established however, with studies to date producing conflicting findings for overall cancer risk and for individual cancers such as breast and prostate cancers.

The QIMR Berghofer study used cancer data drawn from the UK Biobank cohort for more than 46,000 people who had been diagnosed with most invasive cancer types, including about 7,000 people who died from the disease.

The genetic and preference information from the people with cancer was compared to data from more than 270,000 others who had never been diagnosed with cancer.

QIMR Berghofer lead researcher, Jue-Sheng Ong, said the study also looked at some common individual cancers such as breast, ovarian, lung and prostate cancers and found drinking coffee did not increase or decrease their incidence.

“There was some inconclusive evidence about colorectal cancer, where those who reported drinking a lot of coffee had a slightly lower risk of developing cancer, but conversely examination of data from those people with a higher genetic predisposition to drink more coffee seemed to indicate a greater risk of developing the disease,” Mr Ong said.

“The disparity in those findings would suggest more research is needed to clarify if there is any relationship between colorectal cancer and coffee.”

Associate Professor MacGregor said the study had implications for public health messaging around the world.

“The health benefits of coffee have been argued for a long time, but this research shows simply changing your coffee consumption isn’t an effective way of protecting yourself from cancer,” he said.

“The health benefits of coffee have been argued for a long time, but this research shows simply changing your coffee consumption isn’t an effective way of protecting yourself from cancer,” he said.

This article originally appeared here. ACRF has given $8.4M in grants to QIMR Berghofer for cancer research technology since 2002.

Research into an intricate toxin delivery system found in bacteria could overcome the problem of pesticide resistance in insects, and might even lead to new cancer treatments.

An international team led by Dr Michael Landsberg at The University of Queensland has revealed the detailed inner workings of the newest member of a family of naturally occurring insecticidal toxins.

“This toxin, known as YenTc, is a highly effective toxin-delivering nanomachine,” Dr Landsberg said.

“We used a high resolution microscopic imaging method known as electron cryo-microscopy to reveal the complex molecular structure that injects highly toxic molecules into targeted cells, triggering cell death.”

The toxin was isolated from a naturally occurring bacterium that targets many commercially significant insect pest species, including the diamondback moth, and has been earmarked as a new biopesticide.

“We found that YenTc contains unique features which decorate its structure, much like baubles that distinguish the appearance of Christmas trees,” Dr Landsberg said.

“We believe these decorations determine which hosts are susceptible to toxins.

“This selection mechanism will ultimately be crucial to the safety of any future biopesticide technology.

“But understanding it might also allow us to engineer bio-inspired toxins that could be used for therapeutic purposes.”

UQ’s Dr Sarah Piper, said the findings had helped researchers understand why YenTc specifically targeted insects.

“This is an important step, which may eventually allow for YenTc or related toxins to be engineered to target different insect species, or perhaps even selectively target and kill unhealthy cells in animals or people, such as cancer cells, without harming healthy cells,” she said.

“So what began with the goal of trying to prevent insects from destroying vegetable crops might one day lead to us having the capability to design and test new therapeutic approaches for treating cancer.”

The work involved researchers at UQ’s School of Chemistry and Molecular Biosciences and the UQ Institute for Molecular Bioscience, Griffith University, AgResearch New Zealand, the University of Auckland, the University of Basel and the Cambridge Institute of Medical Research.

Original article can be found on the University of Queensland website.

An important component of the microscopic machinery that drives cell death has been identified by Walter and Eliza Hall Institute scientists.

Studying the ‘pro-death’ machinery that forces damaged, diseased or unwanted cells to die, the research team revealed a protein called VDAC2 was critical for the function of a key pro-death protein called Bax.

ACRF has provided $5.1M to WEHI in technology grants since 2001.

The team also showed VDAC2 contributed to the killing of certain cancer cells by anti-cancer agents. The research, published today in the journal Nature Communications, was led by PhD student Dr Hui-San Chin with Professor David Huang, Dr Mark van Delft and Associate Professor Grant Dewson.

Cell Death At a glance

• The death of cells by a process called apoptosis is essential for the removal of unwanted, damaged or diseased cells, and is driven by a finely tuned protein ‘machine’.
• The protein Bax is a key component of the cell death machinery, forming part of a complex that takes cells to a ‘point of no return’ in apoptotic death.
• Our researchers discovered a protein called VDAC2 helps Bax to drive apoptosis, and may have a role in fine-tuning cancer cells’ response to anti-cancer agents.

Driving cancer cell death

A failure of the cell death machinery is a hallmark of cancer cells, and is linked to the resistance of cancer cells to anti-cancer treatments, said Professor Huang.

“Bax is important for helping anti-cancer agents kill cells – without Bax and its relative Bak, cancer cells cannot undergo apoptosis when treated with a range of anti-cancer therapies.

“Our research showed that VDAC2 is required for Bax to drive the response of cancer cells to conventional chemotherapy agents as well as the recently developed BH3-mimetics,” Professor Huang said.

Cell Death machinery

Apoptotic cell death is critical for the development and maintenance of our body, and faults in the protein machinery that drives apoptosis have been linked to a range of diseases. Faulty cell death proteins have been linked to both the development of cancer, as well as resistance of cancer cells to treatment.

A key protein in the cell death machinery is called Bax, Dr van Delft said. “Bax helps to take a cell to a ‘point of no return’ when apoptotic cell death is triggered, forming pores in mitochondria, the powerhouses of the cell. This unleashes the final ‘executioner’ proteins that dismantle a cell.

“Understanding how Bax functions could lead to new therapeutics that either promote cell death – with applications for diseases such as cancer – or therapeutics that prevent cell death, which have the potential to save cells in conditions such as neurodegenerative disorders or stroke,” he said.

The team investigated how Bax and a related protein called Bak kill cells, knocking out the function of different genes using CRISPR technology, Associate Professor Dewson said.

“To our surprise we discovered a gene that was essential for the function of Bax but not Bak, despite these two proteins being functionally and structurally very similar.

“We were able to follow up on this research to show that the protein, called VDAC2, was a catalyst that helped Bax associate with mitochondria and form pores in their membranes, to kill the cell,” Associate Professor Dewson said. “Intriguingly VDAC2’s ‘day job’ is to maintain the function of the mitochondria, pumping metabolites in and out of the mitochondria.”

This article originally appeared on the WEHI website.

Research by the Garvan Institute of Medical Research has revealed a new way to group cancers based on their DNA ‘signatures’.

This release originally appeared on the Garvan Institute’s website.

Every four minutes someone in Australia is diagnosed with cancer. Only one in ten of those diagnosed will exercise enough during and after their treatment. But every one of those patients would benefit from exercise.

I’m part of Australia’s peak body representing health professionals who treat people with cancer, the Clinical Oncology Society of Australia. Today we’re joining 25 other cancer organisations to call for exercise to be prescribed to all cancer patients as part of routine cancer care.

Published today in the Medical Journal of Australia, our plan is to incorporate exercise alongside surgery, chemotherapy and radiotherapy to help counteract the negative effects of cancer and its treatment.

What are we calling for?

Historically the advice to cancer patients was to rest and avoid activity. We now know this advice may be harmful to patients, and every person with cancer would benefit from exercise medicine.

Most doctors and nurses agree exercise is beneficial but don’t routinely prescribe exercise as part of their patients’ cancer treatment plan.

It is our position that all health professionals involved in the care of people with cancer should:

1. view and discuss exercise as a standard part of the cancer treatment plan
2. recommend people with cancer adhere to exercise guidelines
3. refer patients to an exercise physiologist or physiotherapist with experience in cancer care.

Why prescribe exercise?

Cancer patients who exercise regularly experience fewer and less severe side effects from treatments. They also have a lower relative risk of cancer recurrence and a lower relative risk of dying from their cancer.

If the effects of exercise could be encapsulated in a pill, it would be prescribed to every cancer patient worldwide and viewed as a major breakthrough in cancer treatment. If we had a pill called exercise it would be demanded by cancer patients, prescribed by every cancer specialist, and subsidised by government.

Cancer and its treatment can have a devastating effect on people’s lives, causing serious health issues that compromise their physical and mental well-being.

Research shows exercise can help cancer patients tolerate aggressive treatments, minimise the physical declines caused by cancer, counteract cancer-related fatigue, relieve mental distress and improve quality of life.

When appropriately prescribed and monitored, exercise is safe for people with cancer and the risk of complications is relatively low.

Implementing exercise medicine as part of routine cancer care not only has the potential to change people’s lives but to also save money. People with cancer who exercise have lower medical expenses and spend less time away from work.

What exactly should be prescribed?

Exercise specialists can prescribe exercise in a similar way that doctors prescribe medications; by knowing how cancer impacts our health, and understanding how certain exercises improve the structure and function of the body’s systems.

These individualised programs involve specific types of exercises, performed at precise intensities and volumes based on a mechanism of action and dosage needed to counteract the negative effects of cancer.

The evidence-based guidelines recommend people with cancer be as physically active as their current ability and conditions allow. For significant health benefits, they should aim for:

1. at least 150 minutes of moderate intensity aerobic exercise weekly (such as walking, jogging, cycling, swimming)
2. two to three resistance exercise session each week involving moderate to vigorous intensity exercises targeting the major muscle groups (such as weight lifting).

These recommendations should be tailored to the individual’s abilities to minimise the risk of complications and maximise the benefits.

How will patients fill the prescription?

Getting this much exercise may seem out of reach for many people with cancer. But exercise specialists who have experience in cancer care can help. They’ll design an individual program based on the patient’s disease, how they’ve responded to treatment and the anticipated trajectory of their health status.

Online directories can help find accredited exercise physiologists and physiotherapists practising nearby. These services are eligible for subsidies through Medicare and private health insurance.

Or patients can opt for structured cancer-specific exercise medicine programs such as EX-MED Cancer, which I lead. Such programs are designed to maximise the safety and effectiveness of exercise medicine for cancer patient.

Prue Cormie, Principal Research Fellow in Exercise & Cancer, Australian Catholic University

This article was originally published on The Conversation. Read the original article.