Frontiers in Immunology (Oct 2023)

Immunological analysis of hybrid neoantigen peptide encompassing class I/II neoepitope-pulsed dendritic cell vaccine

  • Shinji Morisaki,
  • Shinji Morisaki,
  • Shinji Morisaki,
  • Hideya Onishi,
  • Takafumi Morisaki,
  • Makoto Kubo,
  • Masayo Umebayashi,
  • Hiroto Tanaka,
  • Norihiro Koya,
  • Shinichiro Nakagawa,
  • Kenta Tsujimura,
  • Sachiko Yoshimura,
  • Poh Yin Yew,
  • Kazuma Kiyotani,
  • Yusuke Nakamura,
  • Masafumi Nakamura,
  • Takanari Kitazono,
  • Takashi Morisaki

DOI
https://doi.org/10.3389/fimmu.2023.1223331
Journal volume & issue
Vol. 14

Abstract

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Neoantigens/ are tumor-specific antigens that evade central immune tolerance mechanisms in the thymus. Long-term tumor-specific cytotoxic T lymphocyte activity maintenance requires class II antigen-reactive CD4+ T cells. We had previously shown that intranodal vaccination with class I neoantigen peptide-pulsed dendritic cells (DCs) induced a robust immune response in a subset of patients with metastatic cancer. The present study aimed to perform a detailed ex vivo analysis of immune responses in four patients receiving an intranodal hybrid human leukocyte antigen class II neoantigen peptide encompassing a class I neoantigen epitope (hybrid neoantigen)-pulsed DC vaccine. After vaccination, strong T-cell reactions against the hybrid class II peptide and the class I-binding neoantigen peptide were observed in all four patients. We found that hybrid class II neoantigen peptide-pulsed DCs stimulated CD4+ T cells via direct antigen presentation and CD8+ T cells via cross-presentation. Further, we demonstrated that hybrid class II peptides encompassing multiple class I neoantigen epitope-pulsed DCs could present multiple class I peptides to CD8+ T cells via cross-presentation. Our findings provide insight into the mechanisms underlying hybrid neoantigen-pulsed DC vaccine therapy and suggest future neoantigen vaccine design.

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