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[嵌合抗原受体T细胞疗法治疗急性淋巴细胞白血病]

[CAR T cell therapy in acute lymphoblastic leukemia].

作者信息

Chatterjee Manik, Bargou Ralf C

机构信息

Comprehensive Cancer Center Mainfranken, Interdisziplinäres Studienzentrum mit ECTU, Universitätsklinikum Würzburg, Straubmühlweg 2a, 97078, Würzburg, Deutschland.

Bayerisches Zentrum für Krebsforschung (BZKF), Würzburg, Deutschland.

出版信息

Inn Med (Heidelb). 2025 Jul 15. doi: 10.1007/s00108-025-01949-7.

Abstract

Modern immunotherapy in the form of T‑cell-based CD19-targeted approaches, such as the approved bispecific T‑cell engager (BiTE antibody) blinatumomab and chimeric antigen receptor T cells (CAR T cells) with the approved products tisagenlecleucel and brexucabtagene autoleucel has revolutionized the treatment of B‑precursor acute lymphoblastic leukemia (ALL). The pivotal clinical trials for the approval, including follow-up studies as well as the now available real-world data outside of these trials, showed that CAR-T cell therapy provides an effective treatment option for patients with relapsed and refractory B‑precursor ALL after chemotherapy, improving an otherwise poor prognosis. In addition to the therapeutic response, side effects of CAR-T cell therapy and their clinical management are discussed. Furthermore, resistance mechanisms are discussed and an outlook on further development is given. The T‑precursor ALL remains a challenge due to its immunological complexity but new developments in CAR-T cell treatment approaches targeting CD5 and CD7 show that progress is also being made in this area.

摘要

以基于T细胞的CD19靶向疗法为形式的现代免疫疗法,如已获批的双特异性T细胞衔接器(BiTE抗体)博纳吐单抗,以及已获批产品tisagenlecleucel和brexucabtagene autoleucel的嵌合抗原受体T细胞(CAR T细胞),彻底改变了B前体急性淋巴细胞白血病(ALL)的治疗方式。获批的关键临床试验,包括后续研究以及目前这些试验之外可得的真实世界数据,表明CAR-T细胞疗法为化疗后复发和难治性B前体ALL患者提供了一种有效的治疗选择,改善了原本不佳的预后。除了治疗反应外,还讨论了CAR-T细胞疗法的副作用及其临床管理。此外,还讨论了耐药机制并对进一步发展给出了展望。T前体ALL因其免疫复杂性仍然是一项挑战,但靶向CD5和CD7的CAR-T细胞治疗方法的新进展表明该领域也正在取得进步。

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