Towards effective immunotherapy of cancer using genetically enhanced lymphocytes

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Immunotherapy is a potentially powerful and specific form of cancer therapy that may be more effective and have fewer side effects than current forms of therapy including chemotherapy and radiotherapy. Already dramatic responses have been observed in a proportion of patients receiving immunotherapy for some malignancies but these responses are all too infrequent. T cells constitute an important part of the immune system but they often fail to recognize cancer and do not respond strongly enough against tumours. This project investigates the feasibility of endowing patients' T cells with the abilities to recognize cancer and respond vigorously against it by genetically modifying the T cells. In this study, T cells are removed from mice that have cancer and a gene encoding an anti-cancer molecule inserted into the T cells. The T cells are activated, grown to large numbers and given back to tumour-bearing mice followed by booster vaccinations. The strategy used is novel and the proposed studies, together with preliminary data, represent the first investigations of their type in the world. Information derived from these studies will extend our understanding of tumour immunology and provide an appreciation of the importance of various parameters in achieving anti-tumour responses. Improved anti-tumour responses achieved through investigations in these proof-of-principle pre-clinical models could lead to more effective immunotherapeutic regimens in patients.