Bacterial‐Mediated Tumor Therapy: Old Treatment in a New Context

Abstract

Targeted therapy and immunotherapy have brought hopes for precision cancer treatment. However, complex physiological barriers and tumor immunosuppression result in poor efficacy, side effects, and resistance to antitumor therapies. Bacteria‐mediated antitumor therapy provides new options to address these challenges. Thanks to their special characteristics, bacteria have excellent ability to destroy tumor cells from the inside and induce innate and adaptive antitumor immune responses. Furthermore, bacterial components, including bacterial vesicles, spores, toxins, metabolites, and other active substances, similarly inherit their unique targeting properties and antitumor capabilities. Bacteria and their accessory products can even be reprogrammed to produce and deliver antitumor agents according to clinical needs. This review first discusses the role of different bacteria in the development of tumorigenesis and the latest advances in bacteria‐based delivery platforms and the existing obstacles for application. Moreover, the prospect and challenges of clinical transformation of engineered bacteria are also summarized.

Listeria-based vaccination against the pericyte antigen RGS5 elicits anti-vascular effects and colon cancer protection

“…Longitudinal tumor sizing confirmed trends in improved tumor protection in mice mediating RGS5-specific immunity (Supplementary Figure S2B), indicating the potential utility of this immunotherapeutic approach. Yet, despite this demonstration of general anti-tumor effects, we elected to further our studies by utilizing an RGS5-encoded Lm-based vaccine that provides the following conceptual advantages: [i] Lm instills potent adjuvant effects and selectively infects myeloid cells such as DCs that naturally process and present distinct RGS5 peptides 34 and [ii] a vaccine incorporating various RGS5-presented peptides may help improve protection by instituting epitope spreading against other TME components 35 . From a translational perspective, Lm-based strategies would also not require personalized patient inoculums.…”

Promising dawn in tumor microenvironment therapy: engineering oral bacteria

“…Novyi‐NT spores . 62 , 63 These artificial bacteria not only activate the immune system but also induce local tumor inflammation involving the significantly high expression of proinflammatory factors, 64 such as TNF-α, 65 IL-1β, IL-2, IL-12 66 and IFN-γ. 67 Zhang et al 68 engineered an attenuated strain of Salmonella typhimurium , which has the capability to secrete Vibrio vulnificus flagellin B (FlaB) conjugated with human or mouse interleukin-15 proteins.…”

Deprivation of methionine inhibits osteosarcoma growth and metastasis via C1orf112-mediated regulation of mitochondrial functions

“…Over the last few decades, numerous studies have emerged and re-invigorated the field of bacteria-based bio-therapeutics for the treatment of cancer [ 13 , 14 ]. Indeed, several bacterial genera have been evaluated in pre-clinical cancer models, including Bifidobacterium , Clostridium , and Salmonella enterica serovar Typhimurium [ 15 – 17 ]. As evidenced by the volume of studies in the current literature, Salmonella is by far the most extensively evaluated and characterized bacterial genus currently being explored as a potential modality for bio-therapeutic agent against cancer [ 18 , 19 ].…”