2005 Grants

Research Training Fellowships

Targeting adenoviral suicide gene therapy to intraperitoneal ovarian cancer. Dr Joanne Morrison, John Radcliffe Hospital, Oxford £118,878 over 2 years

LAY TITLE: Improving virus gene therapy for ovarian cancer

Ovarian cancer kills more women in the UK than all of the other gynaecological cancers combined. Most women present at a late stage and, despite radical surgery and chemotherapy, the prognosis has not improved significantly over the past 20 years.

Chemotherapy acts by killing rapidly growing cells, e.g. cancer cells, but also bone marrow cells, the gut lining and hair follicles, causing side effects. The amount of chemotherapy that can be given is limited by these side-effects, and the cancer cells may not receive enough chemotherapy to kill all of them. The more resistant cells survive, the tumour recurs, and may then be resistant to further chemotherapy.

Virus-directed enzyme-prodrug therapy uses a virus to deliver a gene to cancer cells. Once inside cancer cells, the gene makes an enzyme which converts the non-toxic prodrug into a highly active chemotherapy drug. Using this delivery method, the chemotherapy can be targeted directly to cancer cells therefore reducing the side-effects by avoiding normal cells. So far trials in patients have been limited because the virus is neutralised by antibodies, and cancer cells are difficult to infect compared with normal cells.

This project will look at ways of improving the delivery of virus-directed enzyme-prodrug therapy using a polymer to coat the virus. The polymer coating will shield the parts of the virus that normally bind to receptors on cells, therefore inhibiting the normal infection pathway, but will also shield the virus from antibodies. This should enable re-targeting of the virus gene therapy more selectively to cancer cells.

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