干细胞
嵌合抗原受体
生物
持久性(不连续性)
T细胞
免疫学
CD19
抗原
细胞生物学
免疫系统
工程类
岩土工程
作者
Luca Biasco,Natalia Izotova,Christine Rivat,Sara Ghorashian,Rachel Richardson,Aleks Guvenel,Rachael Hough,Robert Wynn,Bilyana Popova,Andre Lopes,Martin Pulé,Adrian J. Thrasher,Persis Amrolia
出处
期刊:Nature cancer
[Springer Nature]
日期:2021-05-24
卷期号:2 (6): 629-642
被引量:64
标识
DOI:10.1038/s43018-021-00207-7
摘要
Low-affinity CD19 chimeric antigen receptor (CAR) T cells display enhanced expansion and persistence, enabling fate tracking through integration site analysis. Here we show that integration sites from early (1 month) and late (>3yr) timepoints cluster separately, suggesting different clonal contribution to early responses and prolonged anti-leukemic surveillance. CAR T central and effector memory cells in patients with long-term persistence remained highly polyclonal, whereas diversity dropped rapidly in patients with limited CAR T persistence. Analysis of shared integrants between the CAR T cell product and post-infusion demonstrated that, despite their low frequency, T memory stem cell clones in the product contributed substantially to the circulating CAR T cell pools, during both early expansion and long-term persistence. Our data may help identify patients at risk of early loss of CAR T cells and highlight the critical role of T memory stem cells both in mediating early anti-leukemic responses and in long-term surveillance by CAR T cells.
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