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Wellcome Trust (UK) announces major international grant for stem cell transplant drug

The consortium is comprised of groups at the University of Auckland, the Peter MacCallum Cancer Centre and Monash University School of Biomedical Sciences in Melbourne, the Queensland Institute of Medical Research in Brisbane, and Medicines Development, is focused around their recent joint groundbreaking research into a protein called perforin, which is a potent toxin generated by killer cells of the immune system.

Professor Joe Trapani, Executive Director of Cancer Research at Peter Mac, who has studied perforin for well over 20 years, notes that while perforin is required to remain healthy, it can also have serious undesired effects, such as when the immune system attempts to rid the body of donated organ tissue or bone marrow following a transplant. In 2010, Professor Trapani, together with ProfessorJames Whisstock’s team at Monash University, unravelled perforin’s molecular structure and confirmed that it destroys cells, by punching large holes in the cell surface.

Dr Julie Spicer, head of the medicinal chemistry team on the project in the Auckland Cancer Society Research Centre (ACSRC) in the Faculty of Medical & Health Sciences at the University of Auckland, who are designing inhibitors of perforin, said “To gain an award from such a prestigious global charity is real recognition both of the quality of our research and the potential of this project to result in tangible benefits for cancer patients”.

Professor Bill Denny, Director of the ACSRC and a member of the research team, said “This is a very exciting project for us, not only because of its novelty and its potential for cancer treatment, but also as another example that NZ science groups can participate at the highest international level”. He noted that early work on the project at the ACSRC was supported by Pre-Seed Accelerator funding from Auckland UniServices, the commercial arm of the University of Auckland.

Drs Spicer and Denny are also members of the Maurice Wilkins Centre (MWC), NZ’s national Centre of Excellence for drug development. Professor Rod Dunbar, Director of the MWC, said “This announcement really represents NZ science at its best – a world-class team based right here, brought into a top-level international project because of their particular skills, to discover new medicines that will help patients world-wide.”

The Dean of the Faculty of Medical & Health Sciences at the University of Auckland, Professor John Fraser, who is an immunologist, said “Winning this award is a major achievement and reflects the very strong science that underpins the clever idea of perforin as a target for immune suppressive therapies. We are very proud that the ACSRC led by Prof. Denny is an integral part of this international team”.

The Chief Executive of the Auckland Cancer Society, Mr John Loof, said “The NZ research community is to be congratulated for its part in securing this significant project. The work is vital if we are to make gains in this area. Yet again our scientists are recognized as being world leaders in their field”.

With an understanding of its molecular structure in-hand and the Wellcome Trust funding, the research teams can now further develop these perforin blocking compounds for testing in humans. The consortium’s first generation of perforin inhibitors has already been shown, by Professor Geoff Hill’s group at the Queensland Institute of Medical Research, to prolong the survival of transplanted bone marrow stem cells in pre-clinical models. If the research team meets the scientific milestones set under the terms of the Wellcome Trust grant, initial clinical trials in human cancer patients will take place by 2016.

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