Scientists have built a new way for CAR-T to accurately intervene in autoimmune diseases

Reporters learned from Beijing Concord Hospital, the hospital Professor Zhang Wei team and Peking University Professor Zhou Demin team, developed based on their own antigen peptides controlled, universal chimed antigen-controlled antigen subject T-cell (CAR-T) technology for the treatment of autoimmune diseases, and the first time in the international application of light-controlled "switch" molecules in CAR-T, to achieve the precise regulation of CAR-T to reduce adverse reactions. The research results were published online in the international authoritative academic journals Rheumatology Yearbook and Cell Chemical Biology.
CAR-T is a new type of cellular immunotherapy. The method is genetically engineered to "navigate" T cells, which can kill target cells with precision and has been widely used in tumor therapy.
, the first author of the paper and a national key laboratory for severe and rare diseases at Beijing Concord Hospital, said that unlike tumors, autoimmune diseases have B cells that secrete a variety of autoantibodies. Targeting the killing of these B cells can effectively reduce their own antibodies, play a therapeutic role. However, whether CAR-T can effectively target its own reactive B cells has not been reported, on the other hand, difficult preparation and low controllability and other issues limit the widespread use of CAR-T. How to build a universal and regulatable CAR-T technology has become an important research direction in this field.
the two teams, after nearly four years of research, first reported the use of autoimmune diseases using autoantigen-specific CAR-T. To solve the problem that traditionally a CAR-T can kill only one cell, researchers have developed a universal CAR-T based on the connecting arm molecule. This is an inert CAR-T that identifies isothione fluorin (FITC). The connecting arm molecule contains FITC and specific antigen peptides, one end can be connected to CAR-T via FITC, and the other end can be targeted by antigen peptides to connect B cells.
"The design is equivalent to upgrading 'only one lock' to 'one key'." Simply changing the antigen end of the connecting arm molecule according to the patient's antibody type allows the target to kill different B cells. Zhang Bo said that in order to further improve safety, avoid cytokine storms caused by CAR-T overactivation, the connecting arm molecules will be upgraded, in which a light-controlled fracture group is introduced, using a "switch" method to accurately regulate the role of CAR-T, equivalent to the "one-size-all key" can be fused at any time.
Zhang said that the series of studies has built a controlled and universal CAR-T platform approach, provided a new technical reserve for safer and more effective CAR-T applications, and provided a new strategy for the precision treatment of autoimmune diseases, with broad prospects for clinical application.