Heat-shock protein-based vaccines for cancer and infectious disease

Almost 60 years ago, the pioneering work of George Klein and others showed that cancers could be made targets for the immune system. Identification of the tumor targets, known as tumor antigens, became a focus in cancer biology that led to the discovery of the immunological properties of heat-shock proteins (HSPs) in 1986 by Pramod Srivastava and colleagues. Since then, the use of HSPs in the therapeutics of cancer and infectious disease in several clinical trials has been guided by our understanding of the role and effects of HSPs in adaptive and innate immune responses, investigated primarily in mice. This review will highlight the immunological properties of HSPs as we understand them today and review the clinical work on human cancers. Several Phase I and II clinical trials in different types of cancer that have been completed, as well as ongoing Phase III trials, will be summarized.