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.

Keywords::

• antigen cross-presentation
• heat-shock protein
• molecular chaperone
• scavenger receptor
• tumor vaccine

Acknowledgements

We acknowledge the support of the Department of Radiation Oncology at Beth Israel Deaconess Medical Center.

Financial & competing interests disclosure

These studies were supported by NIH grants 5RO1CA047407 and 3RO1CA094397 (SKC). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.