a Myeloma Unit, Division of Hematology , University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino , Torino , Italy.
Expert Opin Biol Ther. 2018 Dec;18(12):1209-1221. doi: 10.1080/14712598.2018.1544240. Epub 2018 Nov 13.
Multiple myeloma (MM) is a currently incurable hematologic tumor with heterogeneous clinical behavior and prognosis. During the last years, survival improved due to a better understanding of MM biology and the development of novel drugs, although it still remains unsatisfactory in many cases: new drugs and treatment strategies are needed. CD38 is uniformly expressed at high levels on MM cells and, to a lesser extent, on the surface of normal hematopoietic and non-hematopoietic cells, making this molecule an interesting target for immunotherapeutic approaches.
This review discusses the preclinical and clinical experience on different immunotherapeutic agents targeting CD38 in MM.
Monoclonal antibodies (mAbs) targeting CD38 are currently changing the treatment scenario in MM, allowing physicians to reach unprecedented results, especially when anti-CD38 mAbs are used in combination with consolidated MM treatments. Other immunotherapies targeting CD38 - such as conjugated anti-CD38 mAbs, bispecific antibodies stimulating T cells to eliminate CD38+ MM cells, and CD38-specific chimeric antigen receptor T cells - are interesting strategies, currently at earlier developmental stages.
多发性骨髓瘤(MM)是一种目前无法治愈的血液系统肿瘤,具有异质性的临床行为和预后。近年来,由于对 MM 生物学的更好理解和新型药物的开发,生存情况有所改善,但在许多情况下仍不尽如人意:需要新的药物和治疗策略。CD38 在 MM 细胞表面高水平均匀表达,在程度较小的情况下也在正常造血和非造血细胞表面表达,这使得该分子成为免疫治疗方法的一个有趣靶标。
本文讨论了针对 MM 中 CD38 的不同免疫治疗药物的临床前和临床经验。
针对 CD38 的单克隆抗体(mAbs)目前正在改变 MM 的治疗格局,使医生能够取得前所未有的结果,尤其是当抗 CD38 mAbs 与巩固的 MM 治疗联合使用时。针对 CD38 的其他免疫疗法 - 如结合抗 CD38 mAbs、双特异性抗体刺激 T 细胞消除 CD38+MM 细胞,以及 CD38 特异性嵌合抗原受体 T 细胞 - 是一些有趣的策略,目前处于早期发展阶段。