Current Research:
Major areas of interest are tumour angiogenesis, gene therapy and immunotherapy. Our studies show that patients have a worse prognosis if a tumour has a high vascular density. Tumour types in which we have demonstrated this relationship include common cancers such as breast cancer, lung and bladder cancer, lymphoma and ocular melanoma.

We are testing the potential of antiangiogenic agents to treat patients with solid tumours. Using gene therapy and immunotherapy we have started to focus on malignant melanoma because it is refractory to conventional treatment but can generate specific immuno-responses after cytokine therapy. Immunotherapy requires monitoring to detect whether the treatment has stimulated production of specific cytotoxic T lymphocytes against tumour antigens. In collaboration with Professor V Cerundolo (Molecular Immunology Unit, WIMM, Oxford), we are using a new technique developed at the WIMM to detect antigen specific CTL. This allows our assessment of activity and efficacy of new vaccines.

Future Projects:
The clinical evaluation of antiangiogenic therapy will address four important considerations. Firstly, to assess whether angiogenic pathways have been blocked and blood vessels damaged in vivo, we are developing novel monitoring techniques. Secondly, we are testing single antiangiogenic drugs in tumour types where angiogenesis affects the biological behaviour of the disease. The optimal dose may not be the maximum tolerated dose though it reinforces the need for accurate in vivo monitoring. Thirdly, we may need to use multiple antiangiogenic agents as regulation of angiogenesis complex. Finally, there is experimental evidence for synergy between antiangiogenic agents and other treatment modalities, so we must assess whether the affects of antiangiogenic therapy are optimised when given with chemotherapy or immunotherapy.

Novel methods of vaccine involving priming the immune system with antigens coded by DNA and then using bacterial expressed antigens for boosting the immune response. The use of dendritic cells is being developed. Initially melanoma, but also renal cancer and other common tumour types such as breast cancer or colon cancer will be studied by these methods (prime boost technique).