The quest to create microbial products that can influence cancer outcomes has been re kindled by the mounting evidence of the role that microbiota plays in human health and illness.
Fecal microbiota transplants (FMT), probiotics, naturally colonized bacteria (found surrounding stressed bodily tissues, such as solid tumors), and synthetic bacteria are all considered live biotherapeutics. These categories of live biotherapeutics are being used to treat cancer and are being researched to mitigate side effects through a variety of mechanisms, including immune cell activation, treatment resistance overcome, tumor specificity and killing, inflammation dampening, and therapeutic payload delivery.[1,2,3]
Conventional cancer treatments, including radiation and chemotherapy, can cause systemic side effects, and surgery may not be able to fully remove malignancies, which might result in recurrence. While immunotherapies like CAR-T cell therapy for cancers have improved patient outcomes and therapeutic alternatives, there are still obstacles associated with these treatments, as many of them have a non-localized therapeutic effect and are ineffective against immune-blocking tumors and eliminating the solid tumors. Through the release of cytokines, short-hairpin RNA (shRNA), and tumor associated antigens (TAAs) are certain ways been developed as bacterial therapies that have been designed to stimulate the host immune system via adaptive or innate immune system. Numerous of such treatments focus on both immune system together have the ability to reverse immunosuppression. The next generation of bacterially designed therapeutics has the ability to induce immunological responses in malignancies that evade the immune system and deposit medications directly into tumors. Certain facultative anaerobes, such Salmonella and Listeria are known to selectively target solid tumors and their metastases. Other examples of oncolytic bacteria include as Streptococcus, Serratia species, and Mycobacterium bovis (BCG). Intravesical TICE ® BCG got FDA approval & has been utilized as prophylactic treatment for recurrent tumors in patients with bladder cancer in situ (CIS) and as a treatment for only Stage TaT1 papillary tumors of the bladder that are at high risk of recurrence after careful SWOG 8795 study and the Nijmegen study. [1]
Biomedical application of engineered bacteria
Even though bacteria cannot completely eradicate tumors, they can induce antitumor immunity by expanding within the immune-privileged tumor microenvironment (TME) and decreasing immunosuppression. As a result, the possibility of producing bacteria that carry therapeutic payloads—that is, drugs—may hold great promise in the treatment of cancer. In bacteria-based cancer immunotherapy (BCiT) genetic engineering is used to induce precise and effective antitumor responses. A potent antitumor immune response was elicited by introducing a gene circuit encoding an orthogonal heat switch into the E. coli Nissle 1917 (EcN) strain, which expressed either melanin or tumor necrosis factor-α (TNF-α). In order to create EcN, a temperature-activated genetic switch was incorporated. This switch caused immune checkpoint inhibitors and other therapeutic medicines to be expressed in response to hypothermia (externally triggered) brought on by a brief focused ultrasound treatment (FUS). It is possible to engineer the genetic circuit so that, in response to internal stimuli unique to the tumor, such as a certain pH, oxygen concentration, or glucose gradient in the TME, the bacteria precisely manufacture therapeutic chemicals. QS-responsive compounds, such as acyl-homoserine lactone (AHL), were introduced into E. coli and made to express themselves. These molecules caused bacterial lysis and the subsequent release of therapeutic payload when the bacterial population density within the TME reached a certain threshold. A mixture of gene circuits can be created using a synthetic logic circuit system to react to various input signals and stop leaky expression that results from a single gene circuit. E. coli has been modified to ...
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