Effect of Antibiotic Treatment on Attenuated Salmonella typhimurium VNP20009 Mediated Schwannoma Growth Control

Background/Aim: This study evaluated the effect of enrofloxacin antibiotic treatment on the ability of an attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 to control schwannoma growth in a preclinical mouse schwannoma tumor model. Materials and Methods: The antitumor efficacy of VNP20009 intratumoral (i.t.) injection was assessed in a syngeneic mouse-NF2 schwannoma model, with and without subcutaneous (s.c.) injection of enrofloxacin beginning on day-1 or day-8 post-VNP20009 injection. S. typhimurium colonization was assessed in excised tumor samples following antibiotic treatment. Results: I.t. injection of the VNP20009 significantly decreased the growth of schwannoma tumors in mice compared to PBS-treated controls. Treatment of mice with enrofloxacin on day-1 post-VNP20009 injection resulted in abrogation of VNP20009-mediated tumor growth control. In contrast, tumor growth in i.t. VNP20009-injected mice infused with enrofloxacin beginning on day 8 was significantly decreased compared to i.t. PBS-injected controls. Enrofloxacin significantly reduced the number of viable VNP20009 bacteria in excised tumor samples within one day of antibiotic infusion. Viable bacteria were either few or essentially eliminated at the end of the experiment in antibiotic-treated animals compared to VNP20009-only. Conclusion: Viable VNP20009 can persist for as long as 2.5 weeks following intratumoral injection of schwannoma, during which time tumor growth is retarded. Antibiotic treatment starting 1-day following i.t. VNP20009 abrogated bacterial tumor growth control, whereas initiation of antibiotics 8-days following i.t. VNP20009 was associated with control of tumor growth, albeit less than seen in animals unexposed to antibiotics.