Irradiation conditioning of adjuvanted, autologous cancer cell membrane nanoparticle vaccines

Abstract

Cancer vaccines systems based on autologous cancer cell membrane fragments (CMs) have attracted attention due to broad antigen coverage, however, the lack of immunogenicity of conventional cancer CMs bring the limitations of application. Here, the next-generation nanovaccines is constructed using irradiated cancer cell membrane (RM) coated on a polylactic-co-glycolic acid (PLGA) nanoscale delivery system loaded with a TLR-7 agonist (R837) to generate the [email protected] vaccine with prophylactic and therapeutic anti-cancer properties. Irradiation of cell results in enhanced expression of major histocompatibility complex I (MHCI) on the cell membrane. Compared with regular CMs, RMs carry more 8–11 amino-acid MHC-I epitopes and enrich with more damage-associated molecular patterns (DAMPs). When combined with R837, [email protected] promoted maturation of dendritic cells (DCs) and induced DCs secreting cytokines for immune activation. Following subcutaneous injection in mice, [email protected] accumulated in lymph nodes (LNs) and induced antitumor immune responses which further prevented tumor growth. In addition, [email protected] enhanced the therapeutic efficacy of anti-PD-1 treatment. This work provides a new strategy for improving the antitumor immune response and the efficacy of anti-PD-1 treatment. Taken together, our data showed that irradiation of cancer cells and formulation of RMs into adjuvanted nanoparticles would be a promising strategy for generating autologous cancer vaccines.