A Nanovaccine Based on Adjuvant Peptide FK‐13 and l‐Phenylalanine Poly(ester amide) Enhances CD8+ T Cell‐Mediated Antitumor Immunity

Abstract

AbstractCancer vaccines have shown promise as effective means of antitumor immunotherapy by inducing tumor antigen‐specific T cell immunity. In this study, a novel peptide‐based tumor nanovaccine that boosts antigen presentation and elicits effective antitumor immunity is developed. The adjuvant characteristics of an antimicrobial peptide‐derived core peptide, FK‐13, are investigated and used it to generate a fusion peptide named FK‐33 with tumor antigen epitopes. l‐phenylalanine‐based poly(ester amide) (Phe‐PEA), 8p4, is also identified as a competent delivery vehicle for the fusion peptide FK‐33. Notably, the vaccination of 8p4 + FK‐33 nanoparticles (8FNs) in vivo induces dendritic cell activation in the lymph nodes and elicits robust tumor antigen‐specific CD8+ T cell response. The nanovaccine 8FNs demonstrate significant therapeutic and prophylactic efficacy against in situ tumor growth, effectively inhibit tumor metastasis, and significantly prolong the survival of tumor‐bearing mice. Moreover, 8FNs can incorporate different tumor antigens and exhibit a synergistic therapeutic effect with antiprogrammed cell death protein 1 (PD‐1) therapy. In summary, 8FNs represent a promising platform for personalized cancer vaccines and may serve as a potential combinational modality to improve current immunotherapy.