Chonnam Med J.  2016 Sep;52(3):173-184. 10.4068/cmj.2016.52.3.173.

Targeted Cancer Therapy Using Engineered Salmonella typhimurium

• Zheng JH
• Min JJ

• KMID: 2432267
• DOI: http://doi.org/10.4068/cmj.2016.52.3.173

Abstract

Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

Keyword

Salmonella typhimurium; Genetic Engineering; Neoplasms

MeSH Terms

Animals
Bacteria, Anaerobic
Bifidobacterium
Carcinoma, Squamous Cell
Clinical Trials, Phase I as Topic
Clostridium
Colon
Diagnosis
Escherichia coli
Genetic Engineering
Humans
Melanoma
Mice
Salmonella typhimurium*
Salmonella*

Figure

• 

  FIG. 1 Schematic depiction of Salmonellae-mediated cancer therapy. Attenuated S. typhimurium could be used as a delivery vector to achieve local expression of cargo molecules for cancer therapy. When bacteria are administrated to tumor-bearing animals, the bacterial components recognized by pattern recognition receptors (PRRs) or endogenous danger signals activate the inflammasome pathway, resulting in the secretion of proinflammatory cytokines and inducing cancer cell death. DAMPs: damage-associated molecular patterns, PAMPs: pathogen-associated molecular patterns, TLRs: toll-like receptors.

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