IMMUNOTHERAPY .2. ANTIGENS, RECEPTORS AND COSTIMULATION

To generate a cytotoxic T-lymphocyte (CTL) response to cancer cells re quires tumour-specific antigens appropriately processed and displayed by the MHC proteins; T-lymphocytes with receptors of appropriate speci ficity to recognise these; and initial antigen presentation to the imm une system in an immunogenic context. In vitro, autologous tumour-spec ific CTL have been raised against a number of tumours, thus at least s ome patients have a suitable combination of antigen and receptor. Vacc ination with antigen, or with DNA or viral vectors encoding the antige n, leading to the presentation of identified antigens in an immunogeni c context, can activate T-cells which provide protection from tumour i n animal models. An alternative approach uses gene transfer to T-cells , causing them to express novel receptors which direct their cytotoxic activity towards the tumour. Non-specific immune adjuvants, and expre ssion of novel antigens on tumour cells, are briefly discussed. Recent advances in understanding the requirements for T-cell activation sugg est that failure to efficiently present antigen in an immunogenic cont ext may explain the apparent lack of tumour-specific CTL activation in vivo. In mice, expression of the costimulatory molecule B7-1 on tumou r cells, following gene transfer, allows the modified tumour cells to act as antigen-presenting cells, inducing protective and therapeutic C TL responses in some cases. Clinical trials of some approaches have co mmenced, with some encouraging results which provide a basis for furth er development of immunological gene therapy.