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A cancer drug from the sea

28 June 2011

It is known that white blood cells called T cells can kill tumour cells. Vaccines that stimulate the activity of T cells therefore hold considerable promise as new therapeutic agents.

In 2010, Dr Ian Hermans was awarded $4.5 million from the Health Research Council of New Zealand to engage New Zealand leaders in the fields of immunology, chemistry, oncology and clinical-grade manufacturing, to design, manufacture, and trial new anti-cancer vaccines.

A significant focus of this five-year programme is a melanoma clinical trial that will assess whether the activity of the cancer vaccine can be enhanced by the inclusion of the novel synthetic compound ?-galactosylceramide (?-GalCer). This clinical trial, which will start recruiting patients at the end of 2012, is the culmination of years of extensive preclinical work at the Malaghan Institute.  These studies have shown convincingly that anti-tumour vaccines incorporating ?-GalCer induce significantly stronger anti-tumour responses than those without it.

?-GalCer is a derivative of a natural compound isolated from a marine sponge by the pharmaceutical division of the Japanese Kirin Breweries back in 1993.  It has been reported to have potential in the treatment of several diseases including cancer, malaria, type I diabetes and MS, and equally importantly, has been shown to exert its therapeutic activity via its ability to activate a subset of T cells found in the blood known as invariant natural killer T (iNKT) cells.

The discovery of ?-GalCer was remarkable, and given its considerable therapeutic potential, much effort has been spent in developing robust routes for its synthesis and also to determine exactly how it works.

In order to understand more about how ?-GalCer is able to stimulate immune responses during cancer immunotherapy, Janice Cheng, a PhD student in the Malaghan Institute’s Immunoglycomics Group, devised a highly efficient strategy for producing a specialised version of the compound with a fluorescent probe attached to it.

The advantage of the labelled ?-GalCer, is that it can be ‘seen’ with the appropriate technology, which will enable researchers to gain a better understanding of how it interacts with immune cells to stimulate their anti-tumour activity.

Janice has recently published her work in the international scientific journal Carbohydrate Research, where she describes how the labelled ?-GalCer was made, and importantly, how it is functions just the same as its unlabelled counterpart.  This is important if it is to be an effective molecular tool for studying ?-GalCer function.

Last month we reported that Janice was competing in Victoria University’s 3 Minute Thesis Competition.  We are very happy to inform you that Janice went on to win the Vic International (English as a second language) category, where she was applauded for the effective and engaging way in which she spoke about her research on ?-GalCer.

The collective knowledge gained from using the new ?-GalCer probe, combined with outcomes from basic research being undertaken in the Institute’s Vaccine Research Group with ?-GalCer, will be vital for interpreting the results of the melanoma vaccine clinical trial.

It will also be essential for making informed decisions on how to improve the effectiveness of the cancer vaccine therapy even further.