Probiotics "running errands" deliver immunotherapy safely to the body's anti-cancer "front line"

Recently, Science Translational Medicine, a well-known journal focusing on the transformation of basic research to potential therapy, was published at Columbia University A biomedical engineering research team at University showed that they designed and modified a kind of bacteria, which can directly deliver the drugs for cancer treatment to the tumor, and locally give tumor immunotherapy, so as to achieve the purpose of making immunotherapy safer ▲ this study is expected to reduce the adverse effects of immunotherapy (photo source: Science Translational Medicine) Immunotherapy attacks tumors by activating the body's own immune system, which makes cancer treatment have a revolutionary progress Among them, immunosuppressive checkpoint inhibitors are the key to immunotherapy, which can help immune T cells to relieve inhibition and better recognize and eliminate tumor cells Although immunosuppressive agents have been shown to have a promising effect on many types of cancer, we must be aware that this treatment is not perfect As many as 70% of patients have immune-mediated adverse reactions, including fatigue, rash, endocrine disorders and hepatotoxicity, the researchers said In addition, if the combination of multiple immunotherapies can enhance the effectiveness, it will also increase the risk of adverse reactions, and eventually some patients have to stop taking drugs How to make immunotherapy safer? Considering that immune-mediated adverse reactions are related to the systemic effects of the immune system, Professor tal Danino, who was in charge of the study, envisaged the strategy of "designing and manufacturing a safe probiotic carrier to continuously provide immunocheckpoint therapy in the tumor area, so as to minimize the adverse reactions" The research team led by Professor Danino is dedicated to the transformation of bacteria with the method of synthetic biology It's like a computer program that outputs and writes DNA sequences based on different algorithms, allowing bacteria to produce the molecules people want, including the effective release of cancer drugs This time, the research team designed and modified an Escherichia coli Although some readers may think that the name of E.coli often appears in the news of food poisoning, there are many types of E.coli strains, but most of them are harmless to human body The strain nissle 197 selected by the researchers has been proved to be safe for human body in the past and is a high-quality probiotic After gene transformation, these bacteria have a set of system, which can produce nano antibody, and release the nano antibody after finding the tumor growing in the body These nanoantibodies bind to two anticancer targets: programmed cell death ligand PD-L1 on the surface of tumor cells and CTLA-4 on the surface of cytotoxic T cells Blocking PD-L1 and CTLA-4 can help T cells attack cancer cells ▲ design idea of engineering bacteria (picture source: reference [1]) Next, the researchers tested the probiotic's ability in tumor mice expressing PD-L1 and CTLA-4 checkpoints When the implanted lymphoma grew to a certain volume, the researchers injected the modified bacteria directly into the tumor "Our results show that at least 2 weeks after the treatment, the engineered bacteria still grow and remain functional in mice, and they are confined to the tumor without affecting healthy tissues." Introduction of researchers Under the action of these probiotics, the immune system of mice is activated, which plays an important role in anti-tumor Only a single injection of probiotics, the tumor in mice almost completely subsided, and prevented the metastasis of lymphoma, significantly prolonged the survival of mice In contrast, lymphoma mice that received intraperitoneal injection of clinically relevant antibodies had no such significant effect The authors speculate that "the difference between antibody and probiotic therapy may be that probiotics can continuously antagonize CTLA-4 and PD-L1 in tumors, thus avoiding multiple injections, but multiple injections are very important for the success of antibody therapy." ▲ single injection of modified bacteria (slic-2) in the tumor, the effect of tumor reduction is more obvious than that of clinical related monoclonal antibody (picture source: reference [1]) Using the versatility of probiotic vectors, researchers are further challenging cancer, which is usually less responsive to immunotherapy In the colon cancer mouse model, they combined the bacteria delivering the nano antibody of the immune checkpoint with the bacteria delivering the cytokine, and delivered it locally to the tumor site to strengthen the stimulation of immune cells This probiotic cocktail therapy can also bring the effect of tumor reduction, at the same time, there is no worrying toxic effect Of course, the positive results obtained in animal experiments are only the first step of using bacteria to treat cancer, but it is opening up a new world for future cancer research.