Enhanced Whole Tumor Cell-Based Vaccines by a RAFT and Protein Fusion Strategy for Tumor Immunotherapy

Inactivated whole tumor cell-based vaccines (WTVs) are a promising strategy for tumor immunotherapy, but have exhibited limited antitumor effects clinically. Aiming at constructing enhanced WTVs, we developed glycopolymer-engineered WTVs (G-WTVs) using a Halo-Tag protein (HTP) fusion technique and reversible addition-fragmentation chain transfer (RAFT) polymerization. In our study, G-WTVs with varying molecular weights of glycopolymers were constructed. Compared to unmodified tumor cells, all G-WTVs effectively induced the polarization of macrophages toward the M1 phenotype and promoted the secretion of pro-inflammatory cytokines. This enhanced immune response was attributed to the improved interactions between G-WTVs and the macrophages. Among the G-WTVs, the medium molecular weight variant demonstrated the most pronounced enhancement of antitumor immune responses. Notably, the administration of optimized G-WTVs effectively inhibited the growth of B16 melanoma in mice. Our findings provide a new approach to enhance the antitumor efficacy of WTVs via cell membrane glycopolymer engineering, offering a promising strategy for tumor immunotherapy.