Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

Abstract

Over the years, conventional cancer treatments, such as chemotherapy with only a limited specificity for tumors, have undergone significant improvement. Moreover, newer therapies such as immunotherapy have undergone a revolution to stimulate the innate as well as adaptive immune responses against the tumor. However, it has been found that tumors can be selectively colonized by certain bacteria, where they can proliferate, and exert direct oncolytic effects as well as stimulating the immune system. Bacterial-mediated cancer therapy (BMCT) is now one example of a hot topic in the antitumor field. Salmonella typhimurium is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. This species has been designed and engineered in order to be used in cancer-targeted therapeutics. S. typhimurium can be used in combination with other treatments such as chemotherapy or radiotherapy for synergistic modification of the tumor microenvironment. Considerable benefits have been shown by using engineered attenuated strains for the diagnosis and treatment of tumors. Some of these treatment approaches have received FDA approval for early-phase clinical trials. This review summarizes the use of Salmonella bacteria for cancer therapy, which could pave the way towards routine clinical application. The benefits of this therapy include an automatic self-targeting ability, and the possibility of genetic manipulation to produce newly engineered attenuated strains. Nevertheless, Salmonella-mediated anticancer therapy has not yet been clinically established, and requires more research before its use in cancer treatment.

PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer

“…Compared with monoclonal antibodies and small molecule inhibitors, the use of siRNA to treat tumors requires an effective delivery system. In addition to viral vectors, recent studies have shown that a variety of bacteria can be used as carriers, among which attenuated Salmonella is the most widely studied and applied ( 49 , 50 ). As a vehicle, attenuated Salmonella can carry small hairpin RNA (shRNA ) to a variety of tumor sites, including lung cancer, breast cancer, gastric cancer and prostate cancer.…”

Recent Update on Bacteria as a Delivery Carrier in Cancer Therapy: From Evil to Allies

“…Preclinical data showed a high percentage of bacteria maintained in blood after administration for longer period. Other than that, the limited cytotoxic properties of bacteria requiring conjugation with chemotherapeutic agents as well as the risk of mutation due to genetic modification are also obstacles that need to be overcome to utilise bacteria as a potential therapy in cancer patients ( 5 , 103 , 104 ). On the other hand, BGs has its limitation as a delivery system.…”

The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

“…Modifications regarding synthesis and delivery of anticancer payloads by bacteria are also worth briefly noting. The list of therapeutic payloads continues to grow, with focus placed largely on incorporation or secretion of cytokines, TAA, immune modulators, prodrugs, gene silencers or transport effectors [202,203] (Figure 4). For example, Salmonella avoids detection through use of a modified vacuole, the salmonella-containing vacuole (SCV), allowing time to accomplish replication-which could be exploited as a platform for either continuous drug delivery or to reach therapeutic levels higher than the initial dosage [204,205].…”