Engineered Attenuated Salmonella typhimurium Expressing Neoantigen Has Anticancer Effects

ACS Synth Biol. 2021 Oct 15;10(10):2478-2487. doi: 10.1021/acssynbio.1c00097. Epub 2021 Sep 15.

Abstract

Neoantigen vaccines are an immunotherapy strategy for treating cancer. The vaccine degrades quickly, so the strategy must include protection and precise targeting for immune cell stimulation. In this study, we engineered attenuated Salmonella typhimurium, which is highly infiltrative to tumors, to act as a carrier for Neoantigen peptide vaccine. Our system used a constitutive promoter vector, so that a single injection of Salmonella expressing Neoantigen could be used without requiring additional induction injections. In vivo experiments on bacteria-treated mice showed that Neoantigen expressed by the engineered carrier infiltrated tumors and resulted in suppressed tumor growth, higher survival rates and longer survival times, a relative increase of CD4 and CD8 T cells, and cytokine release. These results indicate that engineered Salmonella can be used as a carrier for Neoantigen immunotherapy.

Keywords: Neoantigen; Salmonella typhimurium; engineered bacteria; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / genetics
  • Antigens / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Genetic Engineering*
  • Immunotherapy / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology*
  • Survival Rate
  • Tumor Microenvironment

Substances

  • Antigens