SCI trans Med: probiotic therapy helps tumor immunotherapy

February 14, 2020 / Biovalley / recently, researchers from Columbia University School of engineering have designed a "probiotic" therapy, which may be expected to improve the safety in tumor immunotherapy, including antibody therapy targeting PD-L1 and CTLA-4 These drugs are released by bacteria and attack the tumor, thus promoting the immune response and eventually leading to tumor regression The study is published today in the journal Science Translational Medicine Immunocheckpoint therapy, such as PD-L1 and CTLA-4, has completely changed the current situation of cancer immunotherapy, and has been successful in some cancers However, systemic injection of these antibodies may cause side effects, with a high proportion of patients reporting adverse reactions In addition, although the combination of these therapies is more effective than the single therapy, they can also produce more serious toxicity In this regard, the team led by TAL Danino, assistant professor of Biomedical Engineering, aims to solve these problems "We want to design a safe probiotic vector that can perform local immunocheckpoint therapy to minimize side effects," said Dr tal Danino, author of the paper and a member of Herbert Owen comprehensive cancer center and Data Science Research Institute "We also hope to expand its versatility by generating a range of immunotherapy combinations, including cytokines that can further trigger anti-tumor immune responses, but it is difficult to systematically administer due to toxicity considerations." Bacterial cancer therapy is not a new idea As early as the 1890s, New York City surgeon William Coley proved that injecting live Streptococcus into cancer patients can achieve the effect of reducing tumor volume Although his method was not widely used due to the radiation therapy invented at the same time, the effect of bacterial therapy can still be seen in the treatment of some cancers For example, doctors have been using the tuberculosis vaccine BCG to treat bladder cancer for decades In recent research, Danino laboratory has created engineering bacteria for bacterial therapy, developed different strain subtypes, treatment methods and gene regulatory elements to effectively release cancer drugs Using the computational model, they first scanned a number of parameters to find the best strain subtype to maximize the drug release in the tumor Finally, the author selected a genetically modified E.coli Strain named "SLIC" "We have shown that modified bacteria do not function in mice until they have grown in mice for at least two weeks and are located inside tumors, thereby preventing the effect of the strain on healthy tissues," gurbatri said The tests in the mouse model further proved that, unlike the previous strains, SLIC can achieve the effect of tumor removal after a single use, so it does not need to inject bacteria many times The team used the probiotic delivery system to release nanoantibodies that block PD-L1 and CTLA-4 in mouse models of lymphoma and colorectal cancer It is well known that tumors express these checkpoints to prevent the immune system, especially T cells, from functioning properly The purpose of blocking PD-L1 and CTLA-4 is to eliminate the "brake signal" and enable T cells to attack cancer Compared with the clinical related antibodies against the same target, probiotic therapy is more effective, which can completely eliminate the tumor and prevent the formation of metastasis in early and late lymphoma mouse models Using the versatility of the system, researchers seek to treat more difficult cancers, such as colorectal cancer, which respond poorly to traditional immunotherapies In this additional model, they paired the immune checkpoint nanoantibodies with cytokines to further stimulate the immune system A single dose of this probiotic mixture can cause tumor regression without side effects being observed Source of information: Designer preliminary treatment for cancer immunology original source: C.R gurbatri El Al., "engineered techniques for local tutorial delivery of checkpoint blockade nanobodies," Science Translational Medicine (2020) STM Scientemag Org / lookup / DOI / scitranslmed.aax0876