CAR-T细胞疗法 z-bo 2020-09-30 313

　　Yvonne Chen, an associate professor at the University of California, Los Angeles and a member of the Johnson Comprehensive Cancer Center, genetically modified immune cells such as T cells to make them attack the most evasive enemy: cancer. The immune cells produced by the new cancer immunotherapy can effectively kill blood cancers, but it is difficult to kill solid tumors.

　　T cells are white blood cells that patrol and attack invaders in our body, but they also need to avoid attacking our own cells. This is a way for cancer to evade surveillance by the immune system. Solid tumors are cancers that form tumor masses in the body, accounting for 90% of cancer cases, and can even inactivate immune cells. These tumors can be surrounded by a protein called transforming growth factor beta (TGF-beta). The protein TGF-β can inhibit the activity of T cells in the tumor environment. Chen discovered a way to help T cells overcome TGF-β inhibition to resist tumor cells.

　　T cells are genetically modified to express a receptor called chimeric antigen receptor (CAR), which is designed to recognize tumor-associated proteins, that is, tumor antigens. Once encountered a cell presenting the target antigen, CAR-T cells can bind to the target cell and kill it. Since CD19 is an antigen found on B cells, T cells (CD19 CAR-T) that can express CARs that target CD19 after genetic modification have been approved by the US Food and Drug Administration (FDA) for the treatment of B-cell leukemia And lymphoma.

　　Although CD19 CAR-T cell therapy has shown encouraging clinical results, sometimes during the entire treatment process, there will be a population of cancer cells without CD19. Chen said, “Clinical trials have shown that 50% of lymphoma patients treated with CD19 CAR-T cells will relapse within 6 months, and many of these cases involve tumor cells that no longer express CD19.” To avoid this, Chen designed T cells that target CD19 and CD20 to reduce the likelihood of any cancer cells evading treatment. This bispecific CAR-T cell therapy is currently being tested in a phase I clinical trial conducted at the University of California, Los Angeles.

　　In addition to blood cancers, solid tumors have always been the focus of many ongoing research work in Chen's laboratory. Chen said, "Immunotherapy works well for hematological tumors, but it is not effective for solid tumors, partly because of the immunosuppression induced by TGF-β." Her new method of using CAR that targets TGF-β after genetic modification is A good start for solid tumors. "TGF-β CAR has shown the potential to safely and effectively enhance the anti-tumor efficacy of T cell therapy."

　　Chen and his colleagues constructed CARs that can respond to TGF-β by enhancing defense capabilities. Chen said, "T cells expressing TGF-β reactive CAR are not inhibited by TGF-β, but are prepared to meet and attack tumor cells when exposed to high concentrations of TGF-β." Chen and His colleagues are developing TGF-β CAR-T cells that also target another tumor-specific marker in order to develop next-generation T cell therapies that can effectively combat immunosuppressive solid tumors.