Heat shock proteins (HSP) are a diverse group of proteins that as molecular chaperones bind to a variety of cell proteins. Administration of the HSP-protein complexes from cancer cells, induces T cell activity against these complexed peptides. Tamura et al used autologous tumor-derived proteins chaperoned by the heat shock proteins in the treatment of cancer. Three different mouse tumor models were used which included spontaneous cancers (lung cancer and melanoma), chemically-induced cancers (fibrosarcoma and colon carcinoma) and spindle cell carcinomas induced by ultraviolet radiation. In all three tumor models, the immunotherapy with the heat shock protein preparations decreased the growth of the primary cancer, the metastatic load and prolonged the life-span. The treatment was effective only when the autologous HSP preparations from the tumors were used and such preparations from tumors other than the autologous cancers were not effective. Such specificity may be due to the distinctness of the antigenic repertoire of each cancer. It is speculated that the antigenic repertoire may result from mutated proteins in cancer. Each mutation takes place randomly, therefore, each cancer harbors a set of distinctly mutated proteins making a repertoire that may be as specific as a fingerprint. Thus, immunotherapy with such unique group of HSP associated proteins, may be the most suitable specific therapy tailored to each individual cancer even without prior knowledge of the identity of such molecular repertoire.

REFERENCE:

Tamura Y et al: Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278, 117-120, 1997

Figure 1: Working model for the dynamic and transient interactions of progesterone receptor with the Hsp90 superchaperone complex (adapted from ref. "U Jakob").