Personalized Vaccination of Tumor-Derived Antigens and STING Agonists for Specific Cancer Immunotherapy.

Abstract

Personalized vaccines have shown their promise in cancer immunotherapy, while screening of personalized antigens remains challenging. Herein, a personalized immunotherapy strategy to treat tumors by its own mechanism is reported, which is achieved through the hydrogel-integrated delivery of tumor-derived antigens and STING signaling activation. Self-assembled nanoparticles composed of gallic acid, manganese ions, and mitoxantrone are prepared to induce immunogenic cell death of tumor cells in vitro to release damage-associated molecular patterns and autologous antigens. Sodium alginate integrated with the released antigens and STING agonists (i.e., MSA-2) can be instantaneously cross-linked with endogenous calcium ions in vivo to form hydrogels upon subcutaneous injection. The hydrogels allow for the controlled release of autologous tumor antigens and agonists to activate specific anti-tumor immune responses via promotion of the maturation of dendritic cells and elicitation of tumor infiltration of cytotoxic T lymphocytes. As a result, the in-situ formation of hydrogel-based vaccines can prevent homologous tumor progression and inhibit metastatic tumor growth. This work outlines a straightforward and generalized strategy for personalized vaccination to enhance cancer immunotherapy.