Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors

Sara Feola, Firas Hamdan, Salvatore Russo, Jacopo Chiaro, Manlio Fusciello, Michaela Feodoroff, Gabriella Antignani, Federica D'Alessio, Riikka Mölsä, Virpi Stigzelius, Paolo Bottega, Sari Pesonen, Jeanette Leusen, Mikaela Grönholm, Vincenzo Cerullo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.

METHODS: Here, we elucidated and exploited innate immune cells to sustain the generation of antigen-specific T cells on the use of our cancer vaccine platform. We explored a previously developed oncolytic adenovirus (AdCab) encoding for a PD-L1 (Programmed-Death Ligand 1) checkpoint inhibitor, which consists of a PD-1 (Programmed Cell Death Protein 1) ectodomain fused to an IgG/A cross-hybrid Fc. We coated AdCab with major histocompatibility complex (MHC-I)-restricted tumor peptides, generating a vaccine platform (named PeptiCab); the latter takes advantage of viral immunogenicity, peptide cancer specificity to prime T-cell responses, and antibody-mediated effector functions.

RESULTS: As proof of concept, PeptiCab was used in murine models of melanoma and colon cancer, resulting in tumor growth control and generation of systemic T-cell-mediated antitumor responses. In specific, PeptiCab was able to generate antitumor T effector memory cells able to secrete various inflammatory cytokines. Moreover, PeptiCab was able to polarize neutrophils to attain an antigen-presenting phenotype by upregulating MHC-II, CD80 and CD86 resulting in an enhanced T-cell expansion.

CONCLUSION: Our data suggest that exploiting innate immunity activates T-cell antitumor responses, enhancing the efficiency of a vaccine platform based on oncolytic adenovirus coated with MHC-I-restricted tumor peptides.

Original languageEnglish
Article numbere008342
JournalJournal for ImmunoTherapy of Cancer
Volume12
Issue number3
DOIs
Publication statusPublished - 8 Mar 2024

Keywords

  • Adaptive Immunity
  • Animals
  • Cytokines/metabolism
  • Humans
  • Mice
  • Neoplasms/therapy
  • Receptors, IgG
  • T-Lymphocytes, Cytotoxic

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