Antibiotic control of tumor-colonizing Salmonella enterica serovar Typhimurium

Area of Science:

• Oncology
• Microbiology
• Immunology

Background:

• Systemic administration of Salmonella enterica serovar Typhimurium (S. typhimurium) demonstrates antitumor effects by preferentially colonizing tumors, leading to shrinkage and clearance.
• However, the use of live bacterial pathogens for systemic therapy raises significant safety concerns.

Purpose of the Study:

• To investigate the safety and efficacy of combining S. typhimurium tumor therapy with early antibiotic treatment using ciprofloxacin.
• To assess the impact of antibiotic intervention timing on tumor regression and the development of antitumor immunity.

Main Methods:

• Tumor-bearing mice were treated with S. typhimurium.
• Systemic administration of ciprofloxacin was initiated at various time points post-infection.
• Tumor growth, clearance, and survival were monitored.
• Antitumor immune responses were evaluated in surviving mice.

Main Results:

• Early administration of ciprofloxacin effectively controlled S. typhimurium colonization.
• This early antibiotic treatment compromised the overall efficacy of tumor therapy, with increased tumor regrowth observed.
• Despite reduced efficacy, some mice achieved tumor clearance even with delayed antibiotic treatment (24h post-infection).
• Mice that cleared tumors despite antibiotic treatment exhibited specific antitumor immune responses.

Conclusions:

• Combining S. typhimurium-mediated tumor therapy with early ciprofloxacin treatment presents a potentially safer therapeutic strategy.
• Enhancing the intrinsic antitumor potency of S. typhimurium is necessary for a more effective combined therapy.
• The development of specific antitumor immunity is a key factor in successful tumor eradication, even under antibiotic treatment.