New Peter Mac-led research, in collaboration with The Australian National University (ANU), suggests a way to possibly fix a failing stem cell transplant in patients with acute myeloid leukaemia (AML).
Each year in Australia around 900 people are diagnosed with AML, a cancer characterised by overproduction of immature white blood cells which impair bone marrow function leading to infections, anaemia, easy bleeding and bruising.
Chemotherapy fails to cure the majority of AML patients, and many require a stem cell transplant. These transplants - requiring a matched bone marrow donor - are often the only chance many AML patients have of a durable remission.
Research led by Dr Kah Lok Chan, who is based in Professor Mark Dawson’s laboratory at Peter Mac, has described in new detail the role that tumour cell MHC class II (MHC-II) plays in the failure of these transplants.
“We’ve known for some time that when MHC-II expression is abnormally silenced in leukaemia cells, transplants are prone to fail and the patient’s cancer returns,” Professor Dawson said.
“Our research has identified a mechanism that can influence MHC-II expression and, in cases where it has been silenced, could turn this back on.”
There is a growing understanding of the role MHC-II plays in how the immune system recognises cancer, and its therapeutic potential.
Drug candidates already exist and the researchers say they could be trialled in AML patients to possibly restore a failing transplant.
The same drug could also have wide applicability in a supportive treatment that improves the effectiveness of a range of anti-cancer immunotherapies.
Lead author Dr Kah Lok Chan said: “For many AML patients, especially those with high-risk disease factors, bone marrow transplantation is the most effective way to treat the leukaemia.”
“Unfortunately, up to 50 per cent of AML patients can relapse after having a bone marrow transplant and these patients then have limited treatment options available to them.”
Associate Professor Marian Burr from ANU, who jointly supervised the research, said cutting-edge CRISPR gene editing technology was used to show a group of proteins, called the CtBP complex, were responsible for switching off MHC-II in AML and other cancers.
“Importantly, we found that inhibiting the CtBP complex using specific drugs restored MHC class II levels and enhanced the ability of immune system cells to destroy the tumour cells,” Associate Professor Burr says.
The paper “Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses” published overnight in Cancer Cell.
For more information contact the Peter Mac Communications team on 0417 123 048.
Peter MacCallum Cancer Centre is a world-leading cancer research, education and treatment centre and Australia’s only public health service solely dedicated to caring for people affected by cancer.
Peter MacCallum Cancer Centre’s Dr Maja Divjak has developed an award-winning animation showing how an innovative new form of cancer treatment targets cancerous cells. Almost 20,000 Australians are diagnosed with a blood cancer each year and researchers at Peter Mac are using CAR T-cell therapy to genetically modify a patient’s blood cells to seek out and kill cancer including some blood cancers.
Peter MacCallum Cancer Centre’s Dr Maja Divjak has developed an award-winning animation showing how an innovative new form of cancer treatment targets cancerous cells.
Almost 20,000 Australians are diagnosed with a blood cancer each year and researchers at Peter Mac are using CAR T-cell therapy to genetically modify a patient’s blood cells to seek out and kill cancer including some blood cancers.
“T cells are naturally occurring white blood cells that form an essential part of the body’s immune system to target and destroy infected cells,” Dr Divjak, a biomedical animator at Peter Mac, said.
“CAR T-cell therapy separates the T-cells from a patient’s blood and re-engineers them in a laboratory by adding special structures called chimeric antigen receptors (CARs) to the surface of the T cells. The modified CAR T-cells are then reinjected into the patient where the specifically engineered receptors can help the T-cells to identify and attack cancer cells in the body.
“The prospect of removing your T-cells, genetically modifying them and putting them back into your system to fight cancer can seem a bit like science fiction and is potentially very frightening for many people.
“We have created a scientifically accurate 3D animation showing T-cells at work and how researchers at Peter Mac are able to change these T-cells so they kill cancer cells.
"The animation magnifies the cells about 8 million times, taking people to the actual cell surface to explain how cancer can evade the immune system and demonstrating how CAR T-cell therapy targets and kills the cancer cells.
“This animation is so helpful in depicting the science it won ‘Best of Show’ for the Science and the Health categories at the Doctors Without Borders Film Festival this year,” she said.
A/Prof Jane Oliaro, Group Leader in the Cancer Immunology Program at Peter Mac, said that while CAR T-cell therapy is proving very effective for some patients with blood cancer, more work is needed.
“My research is focused on improving CAR T-cell effectiveness by incorporating it with a small molecule drug that can directly kill the cancer cells and potentially boost the anti-cancer activity of the CAR T-cells at the same time,” A/Prof Oliaro said
“Unfortunately, some patients fail to respond to CAR T-cell therapy or relapse following treatment and some types of blood cancers haven’t responded as well to CAR T-cell therapy.
“We’re desperate to improve these response rates and have established a Centre of Excellence in Cellular Immunotherapy to help advance the outcomes we’re seeing through this promising treatment,” she said.
Contacts:
For more information contact the Peter Mac Communications team on 0417 123 048.
About Peter Mac
Peter MacCallum Cancer Centre is a world-leading cancer research, education and treatment centre and Australia’s only public health service solely dedicated to caring for people affected by cancer.
Peter Mac has played host to the announcement of an in-principle partnership between the Victorian Government and ground-breaking German biotechnology company BioNTech.
The developers of the Pfizer/BioNTech Covid-19 mRNA vaccine have chosen Victoria to establish their Asia-Pacific mRNA clinical research and development centre which will support researchers to translate their work into medical breakthroughs.
Treasurer Tim Pallas and Minister for Innovation, Medical Research and the Digital Economy Jaala Pulford today announced an in-principle partnership with BioNTech to establish a clinical scale mRNA manufacturing facility in Melbourne.
The arrangement would see BioNTech deliver next-generation mRNA therapeutics and vaccines for research and clinical trials, including infectious diseases, cancer medicines and personalised cancer treatments.
Peter Mac CEO, Professor Shelley Dolan, said the announcement is important for patients with cancer in Australia and around the world.
“Peter Mac’s research extends from fundamental discovery that translates into cancer treatments, providing the perfect opportunity to collaborate with a world leading company such as BioNTech,” Shelley said.
Victorian Treasurer, the Hon Tim Pallas, said: “This is a major coup for Victoria – it will see incredible collaboration opportunities for our researchers and international biotech companies.”
“BioNTech and Moderna are the only companies in the world to deliver mRNA products to market and soon they will both call Victoria home," The Hon Jaala Pulford, the Minister for Innovation, Medical Research and the Digital Economy, said.
Peter Mac scientists have entered a research agreement with Pfizer to better understand how T-cells work and how they can apply that information to explore new treatment avenues.
T-cells are a type of white blood cell that help the immune system fight against foreign substances in the body. They are an important immune response to infection and diseases like cancer.
Over a decade ago research uncovered how we could harness our own T-cells to fight cancer. This led to the development of the innovative CAR T-cell therapy which is used today with remarkable results in some cancers.
This new research will focus on developing a deeper understanding of how T-cells work as well as uncovering mechanisms that will enable us to development new ways to use T-cells to attack cancer.
Led by Professor Ricky Johnstone, Executive Director of Cancer Research at Peter Mac, the project aims to develop new methods to enhance the potency of existing treatments and uncover new means to harness the immune system to fight cancer.
“I am delighted by the support we’re receiving from Pfizer to address the fundamental questions around how T-cells kill cancer cells and identifying the gene expression pathways that regulate this potent immune response,” said Professor Johnstone, who heads the Gene Regulation Laboratory within Peter Mac.
“A deeper understanding of this process could ultimately lead to completely new ways to use T-cells to treat cancer.
“The success of CAR T-cell therapy that uses the help of the body’s T-cells to identify and fight cancer shows the promise of exploring new avenues to genetically modify and harness the power of T-cells to find new cancer therapies,” he said.
The research agreement includes funding support from Pfizer and also provides Peter Mac with access to Pfizer’s library of genetic tools and epigenetic compounds as well as use of high throughput screening capabilities of the Victorian Centre for Functional Genomics based at Peter Mac.
Contacts:
For more information contact the Peter Mac Communications team on 0417 123 048.
About Peter Mac
Peter MacCallum Cancer Centre is a world-leading cancer research, education and treatment centre and Australia’s only public health service solely ded
It was a celebration of the very best of Peter Mac last night, as the annual staff excellence awards winners were announced at the Annual Snapshot event.
Judged by Peter Mac’s Executive team, the seven Peter Mac Award categories reflect Peter Mac’s Strategic Pillars and recognise the winner’s exceptional commitment and contributions.
The team and individual winners illustrate the breadth and quality of work undertaken across clinical, research, and support services at Peter Mac.
The event, held both online and in person for the first time since 2019, also reflected on another busy year at Peter Mac, in which many advancements were made in pursuit of the very best research-led cancer care and treatment.
Director of Peter Mac’s Academic Nursing Unit Professor Mei Krishnasmy delivered the keynote address, sharing her division’s significant achievements across training, education, strategic-planning, and research.
Assistant Minister for Health and Aged Care The Honourable Ged Kearney MP also attended, speaking affectionately about her nursing background and a great admiration for Peter Mac’s work.
Warmest congratulations to all the winners, who were selected from almost seventy entries submitted by colleagues:
Peter Mac Board Director the Honourable Maxine Morand AM, said “The past year at Peter Mac has been one of adaptability, growth, and innovation. While addressing the evolving challenges of responding to the COVID-19 pandemic, I am proud that Peter Mac has maintained a global leadership role in health and research, making continued advances in delivering world’s best cancer care.”
In praising the work of award winners and everybody working at Peter Mac, Chief Executive Professor Shelley Dolan said, “my sincerest thanks and congratulations to all of our Peter Mac people. As I hear from many of our patients, Peter Mac is a very special place – because of all of you.”