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下一代 CAR-T 细胞疗法

英文原题:Next-Generation CAR T-cell Therapies.

查看英文原题

Next-Generation CAR T-cell Therapies.

PubMed 2022/07/06(内容时间) Cancer Discov Q1 · IF 29.5(JCR 2025)

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中文摘要

CD19和B细胞成熟抗原(BCMA)导向的嵌合抗原受体(CAR)T细胞已在部分难治性B细胞和浆细胞恶性肿瘤患者中实现了前所未有的缓解,促使FDA批准其用于治疗白血病、淋巴瘤和骨髓瘤。这些“活体药物”可以成为合成免疫系统的一部分,在某些患者中至少持续存在十年。然而,尽管具有这一巨大影响,血液系统恶性肿瘤和实体癌患者仍存在显著的未满足治疗需求。在本视角中,我们重点介绍近期创新,这些创新推动该领域朝着未来生产更有效和通用的细胞免疫治疗方向发展。下一代CAR-T 细胞将整合基因工程和合成生物学的进展,以增强功能和持久性,并减少治疗相关毒性。自体CAR-T 细胞与旨在靶向免疫抑制性肿瘤微环境的各种异体细胞治疗策略相结合,将拓宽未来CAR-T 细胞治疗的影响。

展开英文摘要原文

CD19- and B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells have enabled unprecedented responses in a subset of refractory patients with B-cell and plasma cell malignancies, leading to their approval by the FDA for the treatment of leukemia, lymphoma, and myeloma. These "living drugs" can become part of a synthetic immune system, persisting at least a decade in some patients.

However, despite this tremendous impact, significant unmet treatment needs remain for patients with hematologic malignancies and solid cancers. In this perspective, we highlight recent innovations that advance the field toward production of a more potent and universal cellular immunotherapy of the future.

Next-generation CAR T cells will incorporate advances in gene engineering and synthetic biology to enhance functionality and persistence, and reduce treatment-associated toxicities. The combination of autologous CAR T cells with various allogeneic cell treatment strategies designed to target the immunosuppressive tumor microenvironment will broaden the impact of future CAR T-cell therapies.

论文信息

作者
Young RM、Engel NW、Uslu U、Wellhausen N、June CH
单位
Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Cancer discovery2022 Jul 6
原文标识
PubMed 35417527 · DOI 10.1158/2159-8290.CD-21-1683