Perforin Inhibitors for the prevention of allogenic bone marrow stem cell transplant rejection

Perforin is a novel and tractable target, the inhibition of which would address significant unmet need in clinical allotransplantation and potentially, a number of other human disorders. An immunosuppressant targeting perforin would provide the first-ever therapy focussed specifically on one of the principal cell death pathways leading to transplant rejection.The Trust has awarded AU$6.8m over three years to Professor Joe Trapani (Peter MacCallum Cancer Centre), Professor Bill Denny (University of Auckland), Professor James Whisstock (Monash University) and Professor Geoff Hill (Queensland Institute for Medical Research) for the development of small molecule inhibitors of perforin that could lead to more prevention of allogeneic bone marrow stem cell transplant rejection and therefore increase survival rates for many forms of cancer. The team led by Professor Joe Trapani, have recently developed three classes of compounds which have been shown to block the action of perforin. Under the Trust funding the team will continue to characterise and improve on these compounds. These inhibitors will be assessed in specific models and then progressed into clinical candidates that could be ultimately assessed in drug trials for indications with significant unmet clinical need.