CART治疗概要1.pptVIP

01 一、 CAR-T * CAR-T Chimeric Antigen Receptor (CAR) T Cell Therapy 嵌合体抗原受体基因修饰的T细胞治疗技术 ——T antibody 抗体修饰的T细胞 ——上世纪80年代至今 一、 CAR-T * A.Engineered T cells expressing CARs can have both therapeutic and adverse effects B.Users-controlled switches.A suicide switch and an on-switch 一、 CAR-T * Several features would be important for an ON-switch CAR design. First, the receptor would still need to be dependent on specific tumor antigen recognition for T cell activation – small molecule alone or antigen alone should not activate. Second, therapeutic activity of the T cell population should be titratable by varying concentration of the small molecule, and at high enough levels, should show an activity comparable to that of conventional CAR T cells. Finally, the timing of CAR T cell response should be reversibly controllable by addition or removal of the small molecule. 一、 CAR-T * C. Molecular strategies to congtrol T cell activation 二、Design of ON-switch CARs * The small molecule thus acts as a priming or licensing factor that is a precondition for antigen-triggered activation. 四、A. Identification of a dual input gated ON-switch CAR construct B. ON-switch CAR architecture is compatible with alternative heterodimerization modules and alternative antigen binding domains * 五、Single molecule imaging shows that two components of the ON-switch CAR only assemble in the presence of small molecule dimerizer * 六、A. ON-switch CAR requires small molecule AND antigen to activate primary human CD4+ T cells B.ON-switch CAR T cells require both antigen and small molecule dimerizer to drive cell proliferation * 六、A.ON-switch CAR requires small molecule AND antigen to activate primary human CD4+ T cells * * 六、 B.ON-switch CAR T cells require both antigen and small molecule dimerizer to drive cell proliferation 01