肿瘤细胞治疗研究
英文原题：Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.
西达基奥仑赛（也称为 cilta-cel）是一种嵌合抗原受体（CAR）T 细胞疗法，靶向 B 细胞恶性肿瘤（如多发性骨髓瘤（MM））癌细胞表面的 B 细胞成熟抗原（BCMA）。
西达基奥仑赛（也称为 cilta-cel）是一种嵌合抗原受体（CAR）T 细胞疗法，靶向 B 细胞恶性肿瘤（如多发性骨髓瘤（MM））癌细胞表面的 B 细胞成熟抗原（BCMA）。它是一种第二代 CAR，其胞外域包含两个 BCMA 结合单链可变片段（ScFv）结构域、一个跨膜结构域，以及一个含有 CD3 和 4-1BB 的胞内域。Cilta-cel 是一种自体、基因编辑的 CAR T 细胞，通过采集并改造受者的 T 细胞，在实验室中制备成患者个性化治疗产品，再回输体内。该 CAR T 细胞产品特别采用带有两个靶向 BCMA 的单域抗体的 CAR，可识别 MM 恶性细胞上表达的两个 BCMA 表位。基于 1b/2 期 CARTITUDE-1 研究的结果，cilta-cel 于 2022 年 2 月 28 日获 FDA 批准，成为复发或难治性（r/r）MM 治疗武器库中的最新成员。它是继 idecabtagene vicleucel（ide-cel）之后第二个获批用于治疗骨髓瘤患者的抗 BCMA CAR T 细胞产品。它在 r/r MM 中诱导早期、深度且持久的缓解，并具有可耐受的安全性特征。接受 cilta-cel 治疗的骨髓瘤患者可能会经历从轻微到危及生命的不良反应，但大多为可管理的毒性。此外，在更长期的患者随访中，其安全性特征保持一致。在 MM 中，cilta-cel 在疗效方面通常优于 ide-cel，但不良事件相当。本综述重点介绍 cilta-cel 疗效、不良事件、与 ide-cel 的比较及其在 MM 治疗中的未来方向的最新进展。
Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3 and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient's T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.
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