Neoantigen
peptides hold great potential as
vaccine candidates for
tumor immunotherapy. However, due to the limitation of
antigen cellular uptake and cross-presentation, the progress with neoantigen
peptide-based
vaccines has obviously lagged in clinical trials. Here, a stapling
peptide-based
nano-vaccine is developed, comprising a self-assembly nanoparticle driven by the
nucleic acid adjuvant-
antigen conjugate. This
nano-vaccine stimulates a strong
tumor-specific T cell response by activating antigen presentation and
toll-like receptor signaling pathways. By markedly improving the efficiency of
antigen/adjuvant co-delivery to the draining lymph nodes, the
nano-vaccine leads to 100%
tumor prevention for up to 11 months and without
tumor recurrence, heralding the generation of long-term anti-
tumor memory. Moreover, the injection of
nano-vaccine with signal neoantigen eliminates the established MC-38
tumor (a cell line of murine
carcinoma of the colon without exogenous OVA
protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling
peptide-based
nano-vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti-
tumor immune response for the neoantigen
peptide-based personalized
tumor immunotherapy.