Synthetic, Supramolecular, and Self-Adjuvanting CD8⁺ T-Cell Epitope Vaccine Increases the Therapeutic Antitumor Immunity

Peptide vaccines are used in clinical cancer immunotherapy, however, they generally suffer from suboptimal immunogenicity compared to live or inactive virus vector vaccines or subunit proteins, leading to limited T-cell immune responses on their own. Here, a synthetic, supramolecular, and self-adjuvanting CD8⁺ T-cell epitope vaccine assembled by the peptide amphiphile conjugated with an epitope derived from tyrosinase-related protein 2 is described. It is found that the obtained hydrogel vaccine on its own stimulates the activation of dendritic cells and elicits comparable therapeutic antitumor efficiency, but a clearly stronger endogenous CD8⁺ T-cell response, compared with the vaccine comprised of peptide, adjuvant and delivery system, which is commonly used in clinic. In addition, combining this novel epitope vaccine with anti-programmed cell death protein 1 (anti-PD-1) therapy significantly improves the therapeutic efficiency against melanoma. The supramolecular assembly approach and the self-assembling peptide should undoubtedly enable a wide range of T-cell epitope vaccines without the additional use of adjuvant and delivery system, and also provide new possibilities for therapeutic peptide delivery for cancer immunotherapy. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim