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

Adv Sci (Weinh). 2023 Jul;10(20):e2300418. doi: 10.1002/advs.202300418. Epub 2023 May 10.

Abstract

Cancer 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.

Keywords: FK-13; Phe-PEA; adjuvant; immunotherapy; tumor nanovaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Amides
  • Animals
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms* / therapy
  • Peptides

Substances

  • Cancer Vaccines
  • Amides
  • Peptides
  • Adjuvants, Immunologic
  • Antigens, Neoplasm