A Versatile Polymer-Based In Situ Nanovaccine to Boost Cancer Immunotherapy

Abstract

In situ vaccination is a promising strategy for personalized cancer immunotherapy; however, its efficacy is often limited by rapid antigen degradation, inefficient delivery to lymph nodes (LNs), and the immunosuppressive tumor microenvironment (TME). To overcome these challenges, we developed a versatile in situ cancer nanovaccine by conjugating the TLR7/8 agonist R848 to a polymeric immunogenic cell death (ICD) inducer, termed G4P-C7A-R848. In aqueous solution, G4P-C7A-R848 self-assembles into nanoparticles (PCR-NPs), which accumulate at tumor sites following systemic administration. Within tumors, PCR-NPs trigger the release of tumor-associated antigens from tumor cells via ICD and subsequently capture them to form an in situ nanovaccine. These nanovaccines then traffic to tumor-draining LNs (TDLNs), where they promote dendritic cell maturation and T cell activation. Moreover, the nanovaccine reprograms macrophages toward the tumoricidal M1 phenotype, thereby alleviating immunosuppression in the TME. This coordinated action enhances the infiltration and activation of CD8⁺ T cells, leading to robust and durable antitumor immunity. Across multiple murine tumor models, PCR-NPs treatment resulted in significant tumor regression and prolonged survival. This study offers a simple yet effective platform for developing potent in situ cancer vaccines.

Keywords

bioactive polymer / cancer immunotherapy / immunogenic cell death / in situ nanovaccines

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RIGHTS & PERMISSIONS

2026 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.