嵌合抗原受体
T细胞受体
细胞疗法
过继性细胞移植
T细胞
抗原
受体
生物
免疫学
免疫疗法
癌症研究
细胞生物学
免疫系统
干细胞
遗传学
作者
Michael C. Jensen,Stanley R. Riddell
摘要
Summary A major advance in adoptive T‐cell therapy ( ACT ) is the ability to efficiently endow patient's T cells with reactivity for tumor antigens through the stable or regulated introduction of genes that encode high affinity tumor‐targeting T‐cell receptors ( TCR s) or synthetic chimeric antigen receptors ( CAR s). Case reports and small series of patients treated with TCR ‐ or CAR ‐modified T cells have shown durable responses in a subset of patients, particularly with B‐cell malignancies treated with T cells modified to express a CAR that targets the CD 19 molecule. However, many patients do not respond to therapy and serious on and off‐target toxicities have been observed with TCR ‐ and CAR ‐modified T cells. Thus, challenges remain to make ACT with gene‐modified T cells a reproducibly effective and safe therapy and to expand the breadth of patients that can be treated to include those with common epithelial malignancies. This review discusses research topics in our laboratories that focus on the design and implementation of ACT with CAR ‐modified T cells. These include cell intrinsic properties of distinct T‐cell subsets that may facilitate preparing therapeutic T‐cell products of defined composition for reproducible efficacy and safety, the design of tumor targeting receptors that optimize signaling of T‐cell effector functions and facilitate tracking of migration of CAR ‐modified T cells in vivo , and novel CAR designs that have alternative ligand binding domains or confer regulated function and/or survival of transduced T cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI