Salmonella as a Promising Curative Tool against Cancer

Abstract

Bacteria-mediated cancer therapy has become a topic of interest under the broad umbrella of oncotherapy. Among many bacterial species, Salmonella remains at the forefront due to its ability to localize and proliferate inside tumor microenvironments and often suppress tumor growth. Salmonella Typhimurium is one of the most promising mediators, with engineering plasticity and cancer specificity. It can be used to deliver toxins that induce cell death in cancer cells specifically, and also as a cancer-specific instrument for immunotherapy by delivering tumor antigens and exposing the tumor environment to the host immune system. Salmonella can be used to deliver prodrug converting enzymes unambiguously against cancer. Though positive responses in Salmonella-mediated cancer treatments are still at a preliminary level, they have paved the way for developing combinatorial therapy with conventional chemotherapy, radiotherapy, and surgery, and can be used synergistically to combat multi-drug resistant and higher-stage cancers. With this background, Salmonella-mediated cancer therapy was approved for clinical trials by U.S. Food and Drug Administration, but the results were not satisfactory and more pre-clinical investigation is needed. This review summarizes the recent advancements in Salmonella-mediated oncotherapy in the fight against cancer. The present article emphasizes the demand for Salmonella mutants with high stringency toward cancer and with amenable elements of safety by virulence deletions.

Nonpathogenic E. coli engineered to surface display cytokines as a new platform for immunotherapy

“…The major novelty of our study is the application of surface display of immune-activating cytokines on the bacterial outer membrane endowing this system to induce potent anti-tumor responses in contrast to the previous bacterial therapy studies using secretion and or self-lysis mediated delivery of biologics to the TME [12][13][14][15]17 . The surface display of biologics in live bacteria leads to significantly enhanced potency not only due to the tumor tropism of the bacteria but also its increased effective concentration due to the two versus three-dimensional mobility [38][39][40] and prolonged half-life in the TME due to its continued biosynthesis by the live bacteria.…”

Colon cancer and cell transformation by clinicalSalmonellastrains are associated with bacterial virulence and intracellular fitness

“…Besides, we previously showed that the overexpression of the proto-oncogene cMYC was required to observe fibroblast transformation after Salmonella infection, using an anchorage-independent growth assay (Scanu et al, 2015), and cMYC is also one of the key players regulating cancer cell metabolism (Dong et al, 2020). Finally, Salmonella tropism towards (pre-)transformed cells suggests a cumulative effect during repetitive exposure (Forbes et al, 2003; van Elsland et al, 2022; Aganja et al, 2022). Thus, repetitive pressure on cell metabolic equilibrium could push the cell toward transformation.…”

Next-Generation Probiotics as Novel Therapeutics for Improving Human Health: Current Trends and Future Perspectives

“…The potential of Salmonella sp. for cancer therapy was highlighted by its ability to localize and proliferate inside tumor microenvironments and often suppress tumor growth [ 84 ]. Salmonella can serve as a unique tool in cancer treatment by delivering toxins that specifically trigger cell death in cancer cells.…”

“…While the positive outcomes of Salmonella -based cancer treatments are in the early stages, they have laid the groundwork for combining these approaches with traditional chemotherapy, radiotherapy, and surgery. This combined strategy holds promise for effectively tackling multi-drug-resistant and advanced-stage cancers [ 84 ]. Additionally, B. pullicaecorum could produce butyrate, a short-chain fatty acid with a variety of gastrointestinal health benefits.…”