肿瘤细胞治疗研究
英文原题：Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity.
嵌合抗原受体（CAR）诱导的转录因子B细胞CLL/淋巴瘤11B（BCL11B）抑制，促进CAR诱导的杀伤（CARiK）细胞从淋巴祖细胞发育。
嵌合抗原受体（CAR）诱导的转录因子B细胞CLL/淋巴瘤11B（BCL11B）抑制可推动CAR诱导的杀伤（CARiK）细胞从淋巴祖细胞发育。在此，我们表明，在人 and 小鼠早期淋巴祖细胞中，CRISPR-Cas9介导的Bcl11b敲除单独或与CAR联合时可差异性地调节该过程。过继转移至造血干细胞受者后，Bcl11b编辑的祖细胞介导了先天样、不依赖抗原的抗白血病免疫反应。在CAR表达允许产生额外抗原特异性反应的情况下，双重编辑的淋巴祖细胞的后代在体内获得了持久的抗白血病活性。这些发现为如何利用Bcl11b靶向定制CAR工程化淋巴祖细胞的抗白血病功能提供了重要见解。
Chimeric antigen receptor (CAR)-induced suppression of the transcription factor B cell CLL/lymphoma 11B (BCL11B) propagates CAR-induced killer (CARiK) cell development from lymphoid progenitors. Here, we show that CRISPR-Cas9-mediated Bcl11b knockout in human and murine early lymphoid progenitors distinctively modulates this process either alone or in combination with a CAR. Upon adoptive transfer into hematopoietic stem cell recipients, Bcl11b-edited progenitors mediated innate-like antigen-independent anti-leukemic immune responses. With CAR expression allowing for additional antigen-specific responses, the progeny of double-edited lymphoid progenitors acquired prolonged anti-leukemic activity in vivo. These findings give important insights into how Bcl11b targeting can be used to tailor anti-leukemia functionality of CAR-engineered lymphoid progenitor cells.
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