Antimelanoma effect of Salmonella Typhimurium integration host factor mutant in murine model

Catierine Hirsch Werle1, Igor Damiani1, Guilherme Paier Milanez1

  • 1Department of Genetics, Evolution & Bioagents, Institute of Biology, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.

Abstract

Insights

Attenuated Salmonella Typhimurium ihfA-null mutants show potential for melanoma treatment. One strain reduced tumor mass but caused toxicity, while another was less toxic but less effective in controlling tumor growth.

Area of Science:

  • Oncology
  • Microbiology
  • Immunotherapy

Background:

  • Cancer immunotherapy leverages biological agents to stimulate anti-tumor immune responses.
  • Salmonella Typhimurium is an opportunistic pathogen that can be engineered for cancer therapy due to its tumor-homing properties.
  • The ihfA gene is crucial for bacterial adaptation and survival, making its null mutants potential candidates for attenuated therapeutic strains.

Purpose of the Study:

  • To evaluate the therapeutic potential of an attenuated Salmonella Typhimurium ihfA-null mutant strain for controlling tumor growth.
  • To assess the efficacy and toxicity of two specific Salmonella strains, LGBM 1.1 and LGBM 1.41, in a murine melanoma model.

Main Methods:

  • Bacterial toxicity was evaluated in vitro and in vivo.
  • C57BL/6JUnib mice were inoculated with B16F10 melanoma cells.
  • Tumor-bearing mice were treated with either LGBM 1.1 or LGBM 1.41 Salmonella strains.

Main Results:

  • The LGBM 1.1 strain demonstrated a reduction in tumor mass but exhibited notable toxic effects.
  • The LGBM 1.41 strain showed reduced toxicity compared to LGBM 1.1.
  • LGBM 1.41 did not significantly reduce tumor mass, offering only a slight initial delay in tumor progression and a modest increase in survival rate.

Conclusions:

  • Salmonella Typhimurium strains with an ihfA-null mutation represent a promising avenue for melanoma treatment.
  • Further research is warranted to optimize Salmonella-based therapies for enhanced efficacy and safety in cancer treatment.