The role of tumor rejection antigens in host antitumor defense mechanisms

Background. Normal cells undergo contact inhibition of growth when their surface molecules interact. Tumor cells, however, have undergone a mutation that prevents this arrest of growth upon contact inhibition and allows constant growth. Thus, growth inhibition fails to occur despite the interaction of surface molecules. In recent years a subgroup of these surface molecules has been of interest to cancer investigators. This subgroup has been termed the tumor rejection antigens (TRAs). As the name implies, these are specific to the tumor of origin and may direct the immune system of the host to target the tumor cells and kill them. Methods. A literature search was carried out on TRAs to ascertain the current thinking on the subject. Results. Initial studies of TRAs have revealed that some of them may be heat shock proteins (HSPs). In particular, grp96, a number of the HSP90 family, has been implicated. More recent studies, however, have shown that HSPs alone may not be immunogenic but may act as carrier proteins for tumor specific peptides. Conclusion. Such findings have led to speculation that HSPs or their associated peptides may have a role in the diagnosis and/or treatment of specific cancers. Immunotherapy and bispecific antibodies in particular are areas in which HSPs may prove to be useful. Cancer 1995;75:2649–55.