Molecular therapy : the journal of the American Society of Gene Therapy · 2025
Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Baatz Franziska, Ghosh Arnab, Herbst Jessica, Polten Saskia, Meyer Johann, Rhiel Manuel, Maetzig Tobias, Geffers Robert, Rothe Michael, Bastone Antonella Lucia, John-Neek Philipp, Frühauf Jörg, Eiz-Vesper Britta, Bonifacius Agnes, Falk Christine S, Kaisenberg Constantin V, Cathomen Toni, Schambach Axel, van den Brink Marcel R M, Hust Michael, Sauer Martin G
Аннотация
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.