PMID: 11912148Mar 26, 2002Paper

Development of a recombinant HSP110-HER-2/neu vaccine using the chaperoning properties of HSP110

Cancer Research
Masoud H ManjiliJohn R Subjeck

Abstract

Several studies have shown that when purified from a tumor, certain heat shock proteins (HSPs) can function as effective vaccines against the same tumor by virtue of their ability to bind tumor-specific peptides. However, only a small fraction of the associated peptides would be expected to be immunogenic, in addition to which, the clinical application of this vaccine requires the availability of a surgical specimen of sufficient quantity for purification of the HSP. The present study describes a new approach for the development of natural HSP vaccines that do not have these limitations. This approach uses a recombinant HSP that is noncovalently bound to a recombinant tumor protein antigen by heat shock. HSP110 has been selected for this purpose, because it has been shown to be a highly efficient molecular chaperone in binding to large protein substrates. We show that a "natural chaperone complex" between HSP110 and the intracellular domain (ICD) of human epidermal growth factor receptor 2 protein (HER-2)/neu is formed by heat shock. This HSP110-ICD vaccine elicited both CD8(+) and CD4(+) T-cell responses against ICD as determined by an antigen-specific IFN-gamma production in an enzyme-linked immunospot assay (ELISPOT). In viv...Continue Reading

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