Salmonella and cancer: from pathogens to therapeutics

Area of Science:

• Oncology
• Microbiology
• Immunology

Background:

• Bacterial cancer therapy, an century-old concept, leverages microbial properties like metabolism and motility for site-specific tumor treatment.
• Unlike passive therapeutics, bacteria can activate tumor-specific immunity, offering a unique approach to cancer treatment.
• Salmonella Typhimurium is a promising bacterial strain evaluated for cancer therapy, acting as both a direct tumoricidal agent and a vaccine vector.

Purpose of the Study:

• To evaluate the safety and anticancer activity of VNP20009, an attenuated Salmonella Typhimurium mutant, in a phase I clinical trial.
• To identify limitations in the clinical development of VNP20009 for bacterial cancer therapy.
• To explore strategies for enhancing tumor colonization of bacterial therapeutics.

Main Methods:

• VNP20009, an attenuated Salmonella Typhimurium mutant, was administered to cancer patients in a first-in-man phase I clinical trial.
• The study assessed the toxicity and anticancer activity of VNP20009.
• Antibody-fragment-based targeting was proposed as a method to improve bacterial tumor colonization.

Main Results:

• VNP20009 demonstrated safety in cancer patients.
• Significant native toxicity against murine tumors was observed.
• Insufficient tumor colonization by VNP20009 was identified as a key limitation for further clinical development.

Conclusions:

• VNP20009 is safe for cancer patients, but its clinical utility is hampered by inadequate tumor colonization.
• Bacterial cancer therapy holds potential, but strategies to improve bacterial delivery and retention within tumors are crucial.
• Antibody-fragment-based targeting presents a potential solution to enhance the efficacy of bacterial cancer therapeutics.