Several G- bacteria including Salmonella Typhimurium and E coli, have been engineered to treat cancers. One of the main things been found is that those bacteria can specifically colonize tumor tissues at a ratio as high as10000:1 over health organs. Bacteria also proliferate selectively throughout tumor tissue. What makes those bacteria specifically target tumor cells?
Every bacteria has its own unique or different mechanism of action against cancer cells. As these are not natural and GMOs, can might express certains factors which directly target cancer specific cells and proliferate in that environment. You can find the details here
https://jcmtjournal.com/article/view/2365/1873
Dear Yijie Daniel Deng,
Bacteria can produce and release bacterial toxins, immune regulatory proteins and proapoptotic proteins specifically into tumors, reducing tumor growth and volume. Bacteria are perfect vessels for targeted cancer therapy. Conventional chemotherapy is limited by passive diffusion, and systemic administration causes severe side effects. Bacteria can overcome these obstacles by delivering therapeutic proteins specifically to tumors. Tumors have several mechanisms to evade detection by the immune system. Bacterial accumulation in tumors creates an infection that attracts immune cells to tumors, overcoming the escape mechanisms of tumors.
Mechanisms
There are five key mechanisms are known to promote preferential bacterial accumulation in tumors.
(i) The immune system is one of the main mechanisms that ensure tumor specificity. Tumors are privileged environments that avoid detection by the immune system, and which allow bacteria to colonize. Tumors evade the adaptive immune system by impairing antigen presentation.
(ii) Other mechanism is the evasion is reduction in level or complete loss of major histocompatibility complex-1 (MHC-1) which is necessary for antigen presentation. Expression of phage lysis protein E in Gram-negative bacteria forms a pore connecting the inner and outer membrane. This pore releases the bacterial cytoplasm and leaves a bacterial membrane shell that can be loaded with therapeutic compounds and proteins.
(iii) Induction of TNF production increases blood flow and entraps bacteria in tumors. Increasing the TNF response has been shown to increase bacterial accumulation and spread in tumors, indicating that controlling the initial inflammation can increase colonization.
(iv) Toll-like receptors (TLR) expressed by cancer cells are activated by bacteria. TLR4 is activated by Gram-negative LPS, and TLR2 is predominantly activated by Gram-positive bacteria. This counterproductive mechanism suggests that adaptation of bacterial LPS to limit TLR activation will increase the efficacy of bacterial cancer treatment.
(v) Bacteria have several secretion mechanisms that can be used for the release of recombinant proteins. Salmonella, for example, uses a Type 3 Secretion System (T3SS) to deliver proteins directly into the cytoplasm of host cells.
Ashish
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