The Cancer and Vascular Biology Group has been working for a number of years on the molecular basis of cell adhesion, cell migration and cell invasion, with a particular emphasis on the immune system, tumour metastasis and the growth of new blood vessels (angiogenesis). Of particular interest has been the role of anionic carbohydrates, such as heparan sulfate, in these processes and the enzyme, heparanase, that degrades heparan sulfate. More recent studies have led to mechanisms of epigenetic control of immune response genes.
In addition the Group aims to apply its basic research findings in cancer and immunology to (i) develop new drugs, notably heparan sulfate mimetics, which inhibit inflammation, cancer spread and angiogenesis and (ii) design clever vaccines for cancer immunotherapy. Considerable amounts of external research funds have been obtained to finance the drug and vaccine discovery programs.
Important discoveries made by the Group are:
- The development of the anti-cancer drug PI-88 (Muparfostat), a heparan sulfate mimetic that prevents tumour metastasis by blocking the endoglycosidase, heparanase, and interferes with the action of growth factors involved in tumour angiogenesis. The drug is well advanced in clinical trials in cancer patients.
- The discovery that heparan sulfate is essential for the normal functioning of the insulin-producing beta cells in the Islets of Langerhans in the pancreas. During Type I diabetes we believe heparanase is delivered by autoreactive T lymphocytes to the islets and the enzyme destroys the heparan sulfate required for beta cell survival. In fact, we believe heparan sulfate replacement therapy represents a viable option for treating this disease.
- The demonstration that heparanase not only acts as an enzyme but can localise within the nucleus of cells and regulate gene expression.
- The discovery that eosinophils, when recruited into tumours by T cells, can induce dramatic tumour regression.
- In collaboration with Dr Joe Altin (Research School of Biology, ANU, the development of a melanoma vaccine (Lipovaxin) that targets dendritic cells and induces a potent anti-tumour immune response. A start-up biotechnology company, Lipotek, has been established to commercialise this technology.
- The Group has discovered a novel form of membrane exchange between cells of the immune system which has the potential to dramatically enhance the immune response against both pathogens and cancer.
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