The role of tumor rejection antigens in host antitumor defense mechanisms

Abstract

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.

Potent antitumor effect elicited by superantigen‐linked tumor cells transduced with heat shock protein 70 gene

“…Heat shock proteins (HSP), highly conserved molecular chaperones, 3,4) can circumvent this dilemma by binding to the entire array of CTL epitopes of the cancer to form HSP-peptide complexes and deliver them to antigen-presenting cells (APC). [5][6][7] Unlike other exogenous antigens, such complexes enter APC and mainly elicit an anti-parent-tumor-specific CTL response by presenting "MHC I-HSP-peptide" complexes on the APC surface for CD8 + T to recognize.…”

The expression of HSP70 and HSP90α in children with Wilms tumor

“…HSPs are highly conserved proteins during evolution [2,3]. They are divided into several major families, hsp110, 90, 70, 60/GaroEL, and the small HSPs based on their size and structure [4][5][6].…”

The Hsp90 chaperone complex-A potential target for cancer therapy

“…In higher organisms their action goes beyond that of a single cell and also affects complex regulatory systems such as the immune response. Hsp90, Grp94 and Hsp70 bind peptides and deliver them to MHC class I molecules, which increases the efficiency of the immune response [58] and often enhance tumor immunogenicity [59] . These pleiotropic functions make Hsp90 chaperone complexes ideal targets for the treatment of cancers.…”