Heat-shock proteins in cancer vaccines: agents of antigen cross-presentation.

Abstract

Heat-shock proteins (HSPs) derived from tumors are capable of eliciting an anticancer immune response by facilitating antigen cross-presentation in antigen-presenting cells (APCs). This process involves the ability of such chaperones to bind tumor antigens and facilitate their uptake by APCs. Recent evidence reveals that HSP-tumor antigen complexes bind cell surface proteins on APCs that mediate complex internalization and antigen-processing events, as well as inducing an innate immune response. Binding of HSPs to surface receptors is, thus, an imposing gateway to the induction of tumor-specific immune responses. Extensive studies in animals have indicated the usefulness of such HSP-based immunotherapy in killing established tumors and causing tumor regression. Currently, one HSP, the endoplasmic reticulum stress-response protein Gp96 is undergoing clinical trials for cancer treatment and has yielded promising results, including the induction of anti-tumor immunity and some benefit for patients when administered as part of a multidose regimen. Future advances in HSP-based immunotherapy will be aided by an understanding of the mechanisms by which HSP-peptide complexes induce innate and adaptive immunity to tumor cells and target the killing of primary and metastatic cancer cells.

• Authors: Ayesha Murshid, Jianlin Gong, Stuart K Calderwood
• Journal: Expert review of vaccines (Expert Rev Vaccines) Vol. 7 Issue 7 Pg. 1019-30 (Sep 2008) ISSN: 1744-8395 [Electronic] England
• PMID: 18767951 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Antigens
• Cancer Vaccines
• Heat-Shock Proteins

Topics

• Animals
• Antigens (immunology)
• Cancer Vaccines (immunology)
• Cross-Priming
• Heat-Shock Proteins (immunology)
• Humans
• Neoplasms (therapy)