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.
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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.