嵌合抗原受体
外域
过继性细胞移植
细胞生物学
信号转导
生物
癌症研究
免疫学
T细胞
免疫系统
医学
受体
遗传学
作者
Emiliano Roselli,Jeremy S. Frieling,Konrad Thorner,María C. Ramello,Conor C. Lynch,Daniel Abate-Daga
出处
期刊:BioDrugs
[Springer Nature]
日期:2019-09-24
卷期号:33 (6): 647-659
被引量:20
标识
DOI:10.1007/s40259-019-00384-z
摘要
The adoptive transfer of genetically engineered T cells expressing a chimeric antigen receptor (CAR) has shown remarkable results against B cell malignancies. This immunotherapeutic approach has advanced and expanded rapidly from preclinical models to the recent approval of CAR-T cells to treat lymphomas and leukemia by the Food and Drug Administration (FDA). Ongoing research efforts are focused on employing CAR-T cells as a therapy for other cancers, and enhancing their efficacy and safety by optimizing their design. Here we summarize modifications in the intracellular domain of the CAR that gave rise to first-, second-, third- and next-generation CAR-T cells, together with the impact that these different designs have on CAR-T cell biology and function. Further, we describe how the structure of the antigen-sensing ectodomain can be enhanced, leading to superior CAR-T cell signaling and/or function. Finally we discuss how tissue-specific factors may impact the clinical efficacy of CAR-T cells for bone and the central nervous system, as examples of specific indications that may require further CAR signaling optimization to perform in such inhospitable microenvironments.
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