Heat-shock protein-based cancer immunotherapy

Abstract

Despite the registration of over 1,000 clinical trials assessing the activity of therapeutic cancer vaccines in human patients with multiple cancer types, only a single vaccine has received FDA approval for clinical use. Nonetheless, the therapeutic potential of immune modulation for treating cancer has continued to be validated with both preclinical and clinical studies, most recently in studies investigating so-called checkpoint inhibitory antibodies targeting CTLA-4 and PD-1. One important class of therapeutic cancer vaccines seeks to generate therapeutic immunity based on the combined adjuvant and antigen delivery characteristics of heatshock proteins. Heat-shock protein-based vaccines are unique among other approaches due to the unique ability of certain heat-shock proteins to dually activate antigen-presenting cells and specifi cally deliver tumor antigens to cytotoxic CD8+ T cells via the antigen cross-presentation pathway. The enclosed chapter provides a comprehensive overview of heat-shock protein-based cancer vaccines assessed in human clinical trials within the context of parallel progress in understanding the interactions between a developing tumor and the human immune system.