Abstract 3536: Caulobacter crescentus as new intravesical treatment for bladder cancer

Abstract

Abstract Introduction and Objectives: The standard of care for high risk non-muscle invasive bladder cancer is the intravesical instillation of Bacillus Calmette-Guérin (BCG), an attenuated strain of the pathogen Mycobacterium bovis, associated with significant side effects often ending treatment prematurely. Using nonpathogenic bacterial strains with anti-tumor activity would thus be beneficial. Caulobacter crescentus is a gram-negative, non-pathogenic fresh water bacterium that does not replicate in a mammalian host and therefore qualifies for having a good bio-safety profile. Caulobacter crescentus has previously been shown to have anti-tumor activity in a model of mammary carcinoma. The aim of this study was to evaluate the anti-tumor activity of intravesical administered Caulobacter cresecentus in an immuno-competent animal model for bladder cancer. Materials and Methods: In vitro, the mouse bladder tumor cell line MBT-2, derived from C3H/He mice, was treated with increasing concentrations of Caulobacter crescentus (C.cresc.). Microscopy and growth assays were performed. In vivo, the same cell line, previously lenti-viral transduced with a luciferase gene (MBT-2 luc), was instilled in the bladder of 6 week old, female C3H/He mice (3×106 cells/50ul). Bioluminescent imaging was performed to determine tumor burden on day 5 and mice were randomized to treatment groups. Intravesical treatments (109 C.cresc. in 50ul of H2O or H2O as control) were performed on days 6, 8, 11 and 15 and tumor growth was examined by bioluminescence after i.p. injection of luciferin. Mice were euthanized on day 20 and mouse bladders processed for histology and immuno-histochemistry. Results: In vivo, intravesical treatment of MBT-2 luc tumor bearing C3H/He mice showed a significant inhibition of tumor growth compared to the control group, while no side-effects due to the intravesical C.cresc. application were observed. Additionally performed in vitro experiments revealed that incubation of MBT-2 cells with C.cresc. resulted in a concentration dependent growth inhibition. Conclusions: These preliminary results support the safety and efficacy of Caulobacter crescentus as a novel intravesical treatment for bladder cancer. Further investigation is needed to reveal the exact mechanism of action and to distinguish, if a direct anti-tumor effect of C.cresc. or the host immune-response is the driving component of the anti-tumor effect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3536. doi:10.1158/1538-7445.AM2011-3536