Xu Shengli, Lam Kong-Peng
Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.
Cancers (Basel). 2020 Apr 23;12(4):1045. doi: 10.3390/cancers12041045.
Multiple myeloma (MM) has emerged as the next most likely oncological or hematological disease indication amenable for cellular immunotherapy. Much of the attention has been focused on B cell maturation antigen (BCMA) as a unique cell surface protein on myeloma cells that is available for monoclonal antibodies, antibody drug conjugates (ADCs), T-cell redirecting bispecific molecules, and chimeric antigen receptor (CAR) T cell targeting. BCMA is a member of the tumor necrosis factor receptor (TNFR) superfamily that binds two ligands B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) and mediates the growth and survival of plasma and MM cells. Interestingly, transmembrane activator and CAML interactor (TACI), another TNFR superfamily member, also binds the same ligands and plays largely overlapping roles as BCMA in normal plasma and malignant MM cells. In this article, we review the biology of TACI, focusing on its role in normal B and plasma cells and malignant MM cells, and also discuss various ways to incorporate TACI as a potential target for immunotherapies against MM.
多发性骨髓瘤（MM）已成为下一个最适合进行细胞免疫治疗的肿瘤学或血液学疾病适应症。目前大部分注意力都集中在B细胞成熟抗原（BCMA）上，它是骨髓瘤细胞上一种独特的细胞表面蛋白，可用于单克隆抗体、抗体药物偶联物（ADC）、重定向T细胞的双特异性分子以及嵌合抗原受体（CAR）T细胞靶向治疗。BCMA是肿瘤坏死因子受体（TNFR）超家族的成员，它结合两种配体，即B细胞活化因子（BAFF）和增殖诱导配体（APRIL），并介导浆细胞和MM细胞的生长与存活。有趣的是，跨膜激活剂和CAML相互作用分子（TACI），另一个TNFR超家族成员，也结合相同的配体，并且在正常浆细胞和恶性MM细胞中与BCMA发挥着基本重叠的作用。在本文中，我们综述了TACI的生物学特性，重点关注其在正常B细胞、浆细胞和恶性MM细胞中的作用，并讨论将TACI作为MM免疫治疗潜在靶点的各种方法。
