Dalla Palma Benedetta, Marchica Valentina, Catarozzo Maria Teresa, Giuliani Nicola, Accardi Fabrizio
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Hematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, 43126 Parma, Italy.
J Clin Med. 2020 Sep 19;9(9):3022. doi: 10.3390/jcm9093022.
B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily, is universally expressed by normal and neoplastic plasma cells and plays a critical role in the proliferation, survival and tumor progression in multiple myeloma (MM). B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have been recognized as proliferation ligands for BCMA in the bone marrow microenvironment. Soluble BCMA levels in the serum correlates with disease phase and tumor burden and is a predictor of progression-free survival (PFS) and overall survival (OS). Recently, the introduction of new monoclonal antibodies against CD38 (Daratumumab and Isatuximab) and SLAM7 (Elotuzumab) has changed the therapeutic approach to MM, improving the response rate and the time to progression, both in newly diagnosed and refractory/relapsed patients. Among the surface antigens on MM cells, BCMA is a suitable target for the design of new antibody-based strategies. Experimental approaches targeting BCMA are currently being investigated and include antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs) and genetically engineered T-cells with chimeric antigen receptors (CAR). In this review we summarize the more recent findings about BCMA biologic rationale as a therapeutic target and report the updated results of preclinical and clinical studies focused on ADCs and bsAbs targeting BCMA.
B细胞成熟抗原（BCMA）是肿瘤坏死因子受体超家族的成员，在正常和肿瘤性浆细胞中普遍表达，在多发性骨髓瘤（MM）的增殖、存活和肿瘤进展中起关键作用。B细胞活化因子（BAFF）和增殖诱导配体（APRIL）已被确认为骨髓微环境中BCMA的增殖配体。血清中可溶性BCMA水平与疾病分期和肿瘤负荷相关，是无进展生存期（PFS）和总生存期（OS）的预测指标。最近，新型抗CD38单克隆抗体（达雷妥尤单抗和isatuximab）和抗信号淋巴细胞激活分子家族成员7（SLAM7）单克隆抗体（elotuzumab）的引入改变了MM的治疗方法，提高了新诊断患者以及难治性/复发性患者的缓解率和疾病进展时间。在MM细胞的表面抗原中，BCMA是设计基于抗体的新策略的合适靶点。目前正在研究针对BCMA的实验方法，包括抗体药物偶联物（ADC）、双特异性抗体（bsAb）和具有嵌合抗原受体（CAR）的基因工程T细胞。在本综述中，我们总结了关于BCMA作为治疗靶点的生物学原理的最新研究结果，并报告了针对BCMA的ADC和bsAb的临床前和临床研究的最新结果。
