CARs and other T cell therapies for MM: The clinical experience.

CARs and other T cell therapies for MM: The clinical experience.
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DOI:
10.1016/j.beha.2018.03.002
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发表时间:
2018-06
期刊:
Best practice & research. Clinical haematology
影响因子:
--
通讯作者:
Smith EL
Smith EL
中科院分区:
其他
文献类型:
--
作者:
Danhof S;Hudecek M;Smith EL

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利用内源性免疫系统来消除恶性细胞一直是一种有趣的方法。在治疗B细胞急性淋巴细胞白血病取得相当大的成功后,嵌合抗原受体(CAR)修饰的T细胞已进入多发性骨髓瘤(MM)领域的早期临床评价。合适的非CD19靶抗原的选择是具有挑战性的,各种骨髓瘤相关的表面分子已在临床前研究。最近的临床方案主要集中在靶向B细胞成熟抗原(BCMA),早期结果很有希望。这些试验在受体结构、患者选择、给药策略和预处理化疗方面有所不同,因此将为最终确定最佳参数铺平道路。MM自体T细胞治疗的其他来源包括亲和力增强的T细胞受体修饰细胞和骨髓浸润淋巴细胞。总之,用于治疗MM的过继性T细胞转移仍处于起步阶段,但如果早期缓解率表明持久性,则将成为MM治疗的一种改变模式的治疗方式。
Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising. The trials differ in receptor constructs, patient selection, dosing strategies and conditioning chemotherapy and will thus pave the way to eventually define the optimal parameters. Other sources for autologous T-cell therapy of MM include affinity-enhanced T-cell receptor-modified cells and marrow infiltrating lymphocytes. In summary, adoptive T-cell transfer for the treatment of MM is still in its infancy, but if early response rates indicate durability, will be a paradigm changing therapeutic modality for the treatment of MM.
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