Division of Hematology, Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium.
Laboratory of Experimental Hematology, Faculty of Medicine & Health Sciences, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
Front Immunol. 2019 Jul 16;10:1613. doi: 10.3389/fimmu.2019.01613. eCollection 2019.
Chimeric antigen receptor (CAR)-modified T cell therapy is a rapidly emerging immunotherapeutic approach that is revolutionizing cancer treatment. The impressive clinical results obtained with CAR-T cell therapy in patients with acute lymphoblastic leukemia and lymphoma have fueled the development of CAR-T cells targeting other malignancies, including multiple myeloma (MM). The field of CAR-T cell therapy for MM is still in its infancy, but remains promising. To date, most studies have been performed with B cell maturation antigen (BCMA)-targeted CARs, for which high response rates have been obtained in early-phase clinical trials. However, responses are usually temporary, and relapses have frequently been observed. One of the major reasons for relapse is the loss or downregulation of BCMA expression following CAR-T therapy. This has fostered a search for alternative target antigens that are expressed on the MM cell surface. In this review, we provide an overview of myeloma target antigens other than BCMA that are currently being evaluated in pre-clinical and clinical studies.
嵌合抗原受体 (CAR)-修饰 T 细胞疗法是一种迅速发展的免疫治疗方法，正在彻底改变癌症治疗。CAR-T 细胞疗法在急性淋巴细胞白血病和淋巴瘤患者中获得的令人印象深刻的临床结果，推动了针对其他恶性肿瘤的 CAR-T 细胞的开发，包括多发性骨髓瘤 (MM)。MM 的 CAR-T 细胞治疗领域仍处于起步阶段，但前景广阔。迄今为止，大多数研究都是针对 B 细胞成熟抗原 (BCMA)-靶向 CAR 进行的，早期临床试验中已获得了较高的缓解率。然而，这些缓解通常是暂时的，经常会观察到复发。复发的一个主要原因是 CAR-T 治疗后 BCMA 表达的丢失或下调。这促使人们寻找在 MM 细胞表面表达的替代靶抗原。在这篇综述中，我们概述了目前正在临床前和临床研究中评估的除 BCMA 以外的骨髓瘤靶抗原。
