CAR-T细胞 z-bo 2020-09-30 305

　　Tumors create an unfavorable environment for immune cells (such as T cells) that fight cancer. In a new study, researchers at the University of North Carolina at Chapel Hill and Jiadong University in Xi’an, China genetically modified genetically modified immune cells to improve the survival and growth of undesirable tumors.

　　The co-author of the paper, Dr. Jean Pietrodotti of the Rheinberg Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, and his research team stimulated immune cells to look for cancer chimeric antigen receptors. We have developed a method of providing signals. (CAR) T cells (CAR-T), after genetic modification, can detect and kill specific cancers---In short, use stimulation signals to make CAR-T cells activated. The results of their preclinical studies provide a new way to make these genetically modified T cells proliferate while avoiding activating other immune cells, which may cause untargeted side effects.

　　The co-author of the paper, Dr. Jan Shu, a postdoctoral assistant researcher at the Laneberg Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, said: It provides growth signals and informs the growth time and location at the same time. Generally speaking, it has little effect on the activity of these T cells.

　　CAR-T cell immunotherapy for solid tumors

　　In CAR-T cell immunotherapy (a type of cellular immunotherapy), T cells are extracted from the patient and genetically modified in the laboratory. Find tumor cells with specific molecular targets on the surface, and then reinject them. Reinject the same patient to fight cancer. Through the clinical immunotherapy program, these researchers designed a new type of experimental CAR-T cell therapy for Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, multiple myeloma, neuroblastoma and leukemia. These CAR-T cell therapies are being tested in clinical trials. Xu Xu said that scientists are trying to find a way to make CAR-T cells effective against solid tumors. After all, solid tumors are not friendly to these genetically modified T cells. Inside solid tumors, T cells cannot make full use of nutrients in the blood to support growth. "One way to improve this situation is to provide these T cells with secondary signals so that they can maintain growth even in very unfavorable environments." First, these researchers discovered the importance of stimulating the function of the molecule IL-23 opinion. They determined that receptors for this stimulus only appear when the anti-cancer T cells are activated. Based on this discovery, they want to know whether T cells can be genetically modified to self-generate this proliferation signal, and it can only be done in anti-tumor T cells.

　　Xu said: "It is possible to selectively provide proliferation signals to T cells that encounter tumors in this way without activating bystander cells in the tumor. By adding T cells, these cells will appear in IL-23 as When T cells are activated, this stimulus promotes proliferation. This method does not affect inactivated T cells."

　　Then, these researchers reported their reactions to them. A method of genetic modification of T cells to produce IL-23. More specifically, they genetically modify these T cells to identify tumors, stimulate it to kill the tumor, and stimulate it to produce IL-23 to help its growth. "When you think about the immune system, it is under very strict supervision. We want to recognize T cell infection or tumor growth and increase the number of tumors. Immunity to infection. I don’t want to have, other specific cells are activated, otherwise the whole body The immune system is activated, which may eventually lead to side effects such as skin allergies. It is expected that only activated T cells (that is, CAR-T cells that encounter tumor cells) will produce these researchers in neuroblastoma and pancreatic cancer mouse models With CAR-. We have identified ways to increase T cell proliferation and find other ways to improve the function of these genetically modified T cells, such as increasing metabolic activity so that they can play a better role in malnourished tumors. They also Plan to continue research.

　　They also believe that this new discovery may improve the experimental CAR-T cell therapy currently being tested in clinical trials. He said that other experimental CAR-T cell designs, such as the CAR-T cell design for pediatric neuroblastoma at the University of North Carolina, have adopted different strategies to enhance CAR-T cells in tumors. This strategy uses a stimulus signal called IL-15.

　　Dotty said: "Currently, experimental CAR-T cell immunotherapy for pediatric neuroblastoma patients. 15. In the preclinical model, IL-23 design is better than IL-15 strategy, so the CAR-T cells used produce The composition of the cytokine IL-15 is different. In the near future, I want to develop this treatment method for solid tumors (such as pancreatic cancer) clinically.