A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity

Nat Commun. 2021 Aug 31;12(1):5195. doi: 10.1038/s41467-021-25506-6.

Abstract

Functional tumor-specific cytotoxic T cells elicited by therapeutic cancer vaccination in combination with oncolytic viruses offer opportunities to address resistance to checkpoint blockade therapy. Two cancer vaccines, the self-adjuvanting protein vaccine KISIMA, and the recombinant oncolytic vesicular stomatitis virus pseudotyped with LCMV-GP expressing tumor-associated antigens, termed VSV-GP-TAA, both show promise as a single agent. Here we find that, when given in a heterologous prime-boost regimen with an optimized schedule and route of administration, combining KISIMA and VSV-GP-TAA vaccinations induces better cancer immunity than individually. Using several mouse tumor models with varying degrees of susceptibility for viral replication, we find that priming with KISIMA-TAA followed by VSV-GP-TAA boost causes profound changes in the tumor microenvironment, and induces a large pool of poly-functional and persistent antigen-specific cytotoxic T cells in the periphery. Combining this heterologous vaccination with checkpoint blockade further improves therapeutic efficacy with long-term survival in the spectrum. Overall, heterologous vaccination with KISIMA and VSV-GP-TAA could sensitize non-inflamed tumors to checkpoint blockade therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Combined Modality Therapy
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Oncolytic Virotherapy
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / immunology*
  • Oncolytic Viruses / physiology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Microenvironment
  • Vaccination
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / immunology*
  • Vesicular stomatitis Indiana virus / physiology
  • Virus Replication

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines