Adoptive transfer of antigen-specific T cells has been most effective in treating cytomegalovirus (CMV) disease and Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD). Both of these diseases develop only during periods of acute immune suppression, and both involve highly immunogenic infected cells, and thus respond well to T cell therapies. In contrast, tumours that develop in the presence of a competent immune system evolve complex immune evasion strategies to avoid and subvert T cell-mediated killing. Therefore, even T cells that display potent cytotoxic activity against tumour cells in vitro may not be effective in vivo without altering the tumour:T cell balance in favour of the T cell. This review discusses several new areas of research aimed at improving adoptive T cell therapy for the treatment of cancer, including the genetic modification of antigen-specific T cells to allow them to perform better in vivo, and conditioning the host to improve in vivo expansion and function of transferred cells.
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