Mimetic Heat Shock Protein Mediated Immune Process to Enhance Cancer Immunotherapy.

ABSTRACT

Inspired by heat shock proteins (HSPs), a self-assembly nanochaperone (nChap) is developed as a novel nanovaccine for boosting antitumor immune responses. Taking advantage of HSP-like microdomains and surface-decorated mannose, this nChap can efficiently capture antigens and ferry them into the dendritic cells (DCs). Subsequently, the nChap can blast lysosomes by transforming the structure and property of surface microdomains, thereby promoting antigen escape and enhancing their cross-presentation in cytoplasm. As a result, the nChap-based nanovaccine can elicit both CD4+ and CD8+ T cell-based immune responses and shows an excellent preventive effect on melanoma. Further combination of the nanovaccine with antiprogrammed death-1 (anti-PD-1) checkpoint blockade offers effective inhibition on the growth of already-established melanoma. Therefore, this nC ap-based nanovaccine provides a simple and robust strategy in mimicking HSPs to realize structure-assisted antigen capture, surface-receptor-mediated DC internalization, and both activation of humoral immunity and cellular immunity, promising for efficient cancer immunotherapy.