Tumour therapy using Salmonella

Abstract

The development of novel therapies that are selective for cancer cells, with limited toxicity to normal tissues, has been a challenge for oncology researchers. Genetically modified Salmonella typhimurium, which is capable of multiplying selectively in tumours and inhibiting their growth, represents a new approach for cancer treatment. Because of its selectivity for tumour tissues, S. typhimurium would also be an ideal vector for delivering therapeutic proteins to tumours. VNP20009, an attenuated strain of S. typhimurium with deletions in msbB and purI genes, possesses desirable attributes, such as low toxicity, tumour-selective multiplication and an intrinsic tumouricidal activity, making it particularly promising. VNP20009 accumulates preferentially in tumours of mice bearing B16F10 melanoma and M019 lung carcinoma. This preferential accumulation also occurs in animals implanted sc. with human tumour xenografts Lox, C8186, DLD1, SW620, HCT116, HTB177, DU145, MDA-MB-231 and Caki. VNP20009 proliferates and accumulates to levels between 1 x 10⁸ and 2 x 10⁹ colony-forming units (cfu)/g tumour after 4 - 5 days, following a single iv. injection of VNP20009 at 1 x 10⁶ cfu/mouse. The amount of VNP20009 accumulating in liver is between 3 x 10⁴ and 2 x 10⁶ cfu/g. VNP20009 also inhibits the growth of a wide spectrum of murine transplantable tumours and human tumour xenografts and is currently undergoing Phase I clinical trials in cancer patients.

• cancer
• salmonella
• vector
• VNP20009