Bacterial anti-cancer breakthrough progress! Effective removal of mouse tumors, human trials are under way.

TextsLi Yuan's creation of "living" medicines is one of the goals of synthetic biologyThese drugs come in many forms, one of which is bacteria, and they are designed to address some of the potential drivers of diseaseOn June 1, Synlogic Therapeutics, a company dedicated to the development of new and transformative drugs, released preclinical development data on SYNB1891, a live biological therapy based on Ecoli, on Nature CommunicationsSYNB1891 is a cancer immunology program developed for the treatment of cancer and is currently being evaluated in clinical Phase I trials for patients with advanced solid or lymphomaThe paper shows that in preclinical cancer models, SYNB1891 therapy can remove tumors and improve anti-tumor immunityThe paper introduces the engineering transformation and characteristics of SYNB1891 in detailPreclinical studies have shown that SYNB1891 has anti-tumor activity in cancer mouse models, produces immune memory, and has a strong activation effect on human antigen-present cells (antigen-cellsing, APC), which is essential for the production of anti-tumor immune responseThe research team used non-pathogenic Ecoli as a platform for developing the SYNB1891 strainEngineered bacterial strains can produce cyclic di-AMP (cyclic di-AMP, CDA) as an irritant to the STING (STimulator of INterferon Genes) pathwayThis mechanism can play a key role in the anti-tumor immune response induced by activating antigen-presenting cells and presenting tumor antigensSYNB1891's bacterial chassis can also potentially increase the strength of the overall immune response by activating the innate immune system through several other mechanisms, including toll-like receptors (TLR)One of the advantages of SYNB1891 is that bacteria do not release STING agonists until they are swallowed by the target cells (antigen-presentcells), so there is a lower risk of harmful effects on other immune cells such as T cellsIn addition, although SYNB1891 is designed to be unable to replicate at will for safety, unless specific nutrients are supplemented, bacteria remain active to activate the local immune response for several days after injection within the tumorIn an open-label, multi-center, dose-increasing clinical Phase I trial (NCT04167137), SYNB1891 is being evaluated as a single therapy in patients with advanced solid tumors or lymphomas Synlogic hopes to publish data on single-drug treatment trials by the end of 2020 After determining SYNB1891 as the maximum tolerable dose for single-drug therapy, Synlogic hopes to launch the second part of this clinical trial, where subjects will receive an increasing dose level of SYNB1891 and a fixed dose of checkpoint inhibitor atezolizumab (Tecentriq®) to determine the recommended dose for the combined treatment Dr Aoife Brennan, President and CEO of Synlogic, said: "SYNB1891 has significant advantages over other methods of targeted delivery and dual immunostimulation This preclinical data highlights the potential for change in SYNB1891, and data from the initial queue of clinical trials have confirmed the feasibility and tolerance of SYNB1891 These results support the continued development of SYNB1891 as a potential treatment option for cancer patients, enabling more patients to benefit from immunotherapy "