TLR7 agonist in combination with Salmonella as an effective antimelanoma immunotherapy

Immunotherapy. 2018 Jun;10(8):665-679. doi: 10.2217/imt-2017-0188. Epub 2018 Mar 22.

Abstract

Aim: We evaluated a novel approach combining the use of attenuated Salmonella immunotherapy with a Toll-like receptor agonist, imiquimod, in B16F1 melanoma-bearing mice.

Materials & methods: B16F1 melanoma-bearing mice were daily treated with topical imiquimod in combination with one intratumoral injection of attenuated Salmonella enterica serovar Typhimurium LVR01.

Results: The combined therapy resulted in retarded tumor growth and prolonged survival. Combination treatment led to an enhancement in the expression of pro-inflammatory cytokines and chemokines in the tumor microenvironment, with a Th1-skewed profile, resulting in a broad antitumor response. The induced immunity was effective in controlling the occurrence of metastasis.

Conclusion: Salmonella LVR01 immunotherapy in combination with imiquimod is a novel approach that could be considered as an effective antimelanoma therapy.

Keywords: Salmonella; experimental model; imiquimod; immunotherapy; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Death
  • Cell Line, Tumor
  • Female
  • Imiquimod / therapeutic use
  • Immunotherapy / methods*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / microbiology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Microbial Viability
  • Neoplasm Metastasis / prevention & control
  • Salmonella typhi / immunology*
  • Salmonella typhi / physiology
  • Survival Analysis
  • Toll-Like Receptor 7 / agonists*
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Imiquimod