Immunotherapy With CTL Restricted by Nonself MHC

In the past years a number of target antigens recognized by cytotoxic T-lymphocytes (CTL) have been identified in human malignancies. In most cases, the CTL-recognized antigens did not arise from mutations, but were instead encoded by genes that were identical in normal and tumor cells. Gene expression in normal tissues may result in tolerance of high avidity CTL, leaving behind low avidity CTL that cannot provide effective immunity against tumors expressing the relevant target antigens. In this chapter we describe a strategy to circumvent immuno-logical tolerance that can be used to generate high avidity CTL against self-proteins, including human tumor-associated antigens.