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Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
Myeloid-lineage CAR knockin mice enable allogeneic immunotherapy for liver and lung fibrosis
Min Wang1, Yaoyang Zhang2, Qinyao Zhu2
1Department of Respiratory and Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, China; Roc Rock Biotechnology (Suzhou) Co., Ltd., Suzhou 215000, China.
Abstract:
The preparation of chimeric antigen receptor immune cells (CAR-ICs) typically involves a costly and time-intensive process. Moreover, the transduction of CAR genes into ICs, particularly macrophages, presents inherent challenges. Here, we report a novel strategy to obtain CAR-modified macrophages (CAR-Ms) directly from living animals to treat pulmonary and hepatic fibrosis. We first validated adenovirus-transduced CAR-Ms targeting fibroblast activation protein (FAP) in vitro, as well as in mouse models of pulmonary and hepatic fibrosis. Using a Cre/LoxP strategy, we generated mice with myeloid-specific expression of FAP-CAR, which showed inherent resistance to induced fibrosis. Furthermore, transplantation of macrophages or allogeneic transfusion of whole blood from these transgenic mice alleviated fibrosis in recipient mice. This proof-of-concept study sourcing gene-modified ICs directly from living animals shows promise as a therapeutic platform to treat various diseases.
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