By harvesting nanovesicles derived from DCs that were transduced with recombinant adenovirus to induce expression of multiple antigen epitopes on MHC I, transmembrane-anchored anti-PD-1 scFv, and B7 costimulatory molecules simultaneously, Liu and Liu et al. created a nanovaccine that spatiotemporally combined various signals. The nanovaccine enriched in LNs upon s.c. injection into mice, elicited polyfunctional and antigen-specific CD8+ T cells, decreased the frequency of dysfunctional PD1+CD38+CD8+ T cells among TILs, led to complete tumor regression that was dependent on co-delivery of B7 and anti-PD-1, and induced immunological memory.
Contributed by Ute Burkhardt
ABSTRACT: The strategy of combining a vaccine with immune checkpoint inhibitors has been widely investigated in cancer management, but the complete response rate for this strategy is still unresolved. We describe a genetically engineered cell membrane nanovesicle that integrates antigen self-presentation and immunosuppression reversal (ASPIRE) for cancer immunotherapy. The ASPIRE nanovaccine is derived from recombinant adenovirus-infected dendritic cells in which specific peptide-major histocompatibility complex class I (pMHC-I), anti-PD1 antibody and B7 co-stimulatory molecules are simultaneously anchored by a programmed process. ASPIRE can markedly improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumours. This work presents a powerful vaccine formula that can directly activate both native T cells and exhausted T cells, and suggests a general strategy for personalized cancer immunotherapy.