A $6.8 million award will support Australian and New Zealand scientists in the development of a new class of immune-suppressive drugs to protect bone marrow stem cell transplants in cancer patients.
Bestowed by the Wellcome Trust (UK), the award will allow researchers from the Peter MacCallum Cancer Centre (Peter Mac), The Auckland Cancer Society Research Centre, Monash University and the Queensland Institute of Medical Research to capitalise on groundbreaking research into the perforin protein, a powerful toxin expressed by killer cells of the immune system.
Transplantation of bone marrow from a family member or an unrelated donor restores vital platelet and white blood cell levels in patients with lymphoma or leukemia after treatment with high-dose chemotherapy. However, the immune system can reject the ‘foreign’ transplanted tissue. Perforin is key to this process.
Project leader, Professor Joe Trapani, Executive Director of Cancer Research at Peter Mac, who has studied perforin for well over 20 years, said that while perforin is required to remain healthy, it can also have serious undesired effects.
“If we don’t make enough perforin, the body can’t effectively fight off many viruses. But perforin can also mark the wrong cells for elimination, such as when the immune system attempts to rid the body of donated organ tissue or bone marrow following a transplant,” Professor Trapani said.
In 2010, Professor James Whisstock of Monash University’s School of Biomedical Sciences and his team collaborated with Peter Mac researchers to determine the molecular structure of perforin.
Now, with an understanding of its molecular structure in-hand and the Wellcome Trust funding, the research teams can further develop perforin-blocking compounds for testing in humans.
“It's just fantastic to have the opportunity to deploy a basic science discovery such as the perforin structure in a drug development program," Professor Whisstock said.
Queensland Institute of Medical Research’s Professor Geoff Hill said the first generation of perforin inhibitors had been shown to prolong the survival of bone marrow stem cells in his pre-clinical models.
"If we can translate these results into humans, a greater number of cancer patients will be able to undergo stem cell transplantation, as the perforin inhibitor will enable them to be matched with more varied donors," Professor Hill said.
If the research team meets the scientific milestones set under the terms of the Wellcome Trust award, it aims to progress to clinical trials by 2016.
The perforin inhibitor project is funded under the Wellcome Trust’s Seeding Drug Discovery Initiative.