Future of Bacterial Therapy of Cancer

Abstract

Bacterial therapy of cancer has a centuries-long history and was first-line therapy at the hospital in New York City that would become Memorial Sloan-Kettering Cancer Center, under Dr. William B. Coley. However, after Coley's death in 1936, bacterial therapy of cancer ceased in the clinic until the present century. Clinical trials have been recently carried out for strains of the obligate anaerobe Clostridium novyi with the toxin gene deleted, and on an attenuated strain of Salmonella typhimurium (S. typhimurium), which is a facultative anaerobe that can grow in viable, as well as necrotic, areas of tumors, unlike Clostridium, which can only grow in the hypoxic areas. Our laboratory has developed the novel strain S. typhimurium A1-R that is effective against all tumor types in clinically-relevant mouse models, including patient-derived orthotopic xenograft (PDOX) mouse models. This chapter suggests future clinical applications for S. typhimurium A1-R.

Keywords: Amino acid; Auxotroph; Cancer; Cell cycle; Combination chemotherapy; Decoy; Fluorescence ubiquitination-based cell cycle indicator (FUCCI); Green fluorescent protein (GFP); Imaging; Metastasis; Mouse models; Nude mice; Orthotopic; Salmonella typhimurium A1-R; Surgical orthotopic implantation (SOI); Tumor-targeting.