J. Clin. Invest. 110: 289–294 (2002). doi: 10.1172/JCI200216216. called reverse immunology method, specifically by sensitizing immune cells with the candidate antigen, then testing the ability of sensitized cells to specifically kill tumor cells that are known to express the antigen. To date, approximately 70 MHC class I–and class II–associated tumor antigens have been discovered, while more than 1,700 have been identified by antibodies in cancer patients. About ten antigens are currently known to be recognizable by both T cells and antibodies, although the actual number of antigens for which IgG production requires Th cells is probably much greater.

We do not know for certain how many of the candidate tumor antigens are suitable targets for tumor immunotherapy. A “valid” target antigen must be expressed specifically in the tumor, or at least be expressed at levels sufficiently higher there than in vital organs. For T cell–based therapy, it must be processed and presented in the context of MHC molecules. The need for positive and negative control tumor lines is often overlooked; rigorous (and numerous) controls are needed to convincingly demonstrate that a candidate antigen is a suitable target for use in an immunotherapy trial.