Tumor Secreted Grp170 As a Cancer Vaccine: Tumor Secreted Grp170 Chaperones Tumor Antigens to the Tumor Microenvironment and Induces an Adaptive Anti-tumor Immune Response

Grp170 is a major molecular chaperone/stress protein resident in the ER. It is distantly related in sequence to both hsp110 and hsp70 families. Although most chaperones are intracellular proteins they can be modified into secretory proteins. Chaperones secreted into the tumor microenvironment can recruit professional APCs and promote antigen presentation and priming of T-lymphocytes. This book describes an approach to target grp170 to the tumor microenvironment, which results in tumor rejection mediated by an adaptive immune response that is CD8+ dependent and accompanied by an enhanced cellular immune response against a tumor-specific antigen. Furthermore, the secreted grp170 is shown to deliver full-length tumor antigens to the tumor microenvironment. This approach has the potential of being exploited clinically as a cancer-specific vaccine in tumors of various histological origins.