Targeted Cancer Therapy Using EngineeredSalmonella typhimurium

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.

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

“…Particularly, Salmonella enterica serovar Typhimurium ( S . Typhimurium) has shown to be highly effective as an agent in many types of cancers in both preclinical and clinical models, with a demonstrated safety profile ( 18 ).…”

Nontyphoidal Salmonella : a potential anticancer agent

“…; Chavez‐Navarro et al . ; Zheng and Min ). A number of recent reviews have illustrated this role of Salmonella quite elaborately (Wang et al .…”

Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities

“…Bacteria can be used in theranostics because they can specifically target tumors and can replicate in tumor cells . The ease of genetic manipulation of bacteria allows for the production of attenuated strains with greater safety profiles, and vector systems, thereby allowing for precise tuning and multifunctional capabilities . To facilitate the monitoring of migration patterns and to follow the proliferation of these bacteria, scientists use genetically modified bacteria to express reporter genes that allow optical imaging .…”

“…To facilitate the monitoring of migration patterns and to follow the proliferation of these bacteria, scientists use genetically modified bacteria to express reporter genes that allow optical imaging . In addition, bacteria can be detected by MRI or PET . Sheng‐Nan Jiang et al, used an E coli strain K‐12 (MG1655) producing the cytotoxic protein and pore‐forming hemolytic cytolysin A (to kill colon cancer cells) and the bacterial luciferase ( Lux ) operon (as an in vivo imaging marker).…”