B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches.
多发性骨髓瘤中的 b细胞成熟抗原 (BCMA): 靶向的基本原理和当前的治疗方法。

摘要

Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM. Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated. B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM. Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations. Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments. These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM. Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM.

译文

尽管在过去的十年中,多发性骨髓瘤 (MM) 的治疗取得了相当大的进步,但很大一部分患者对目前的治疗没有反应或反应持续时间短。此外,这些治疗可能具有显著的发病率,并且并非所有患者都一致耐受。由于 MM 没有治愈方法,患者最终会对治疗产生耐药性,导致复发/难治性 MM 的发展。因此,存在对具有新的作用机制的 MM 治疗的未满足需求,这些机制可以提供持久的反应,逃避对先前治疗的抵抗,和/或具有更好的耐受性。B细胞成熟抗原 (BCMA) 由成熟的 B 淋巴细胞优先表达,其过表达和激活与临床前模型和人类的 MM 有关, 支持其作为 MM 治疗靶点的潜在效用。此外,BCMA 作为 MM 生物标志物的使用得到了其预后价值、与临床状态的相关性以及其用于传统上难以监测的患者群体的能力的支持。在这里,我们回顾了在 MM 治疗中用于靶向 BCMA 的三种常见治疗方式: 双特异性抗体构建体、抗体-药物结合物和嵌合抗原受体 (CAR) -改良的 T 细胞疗法。我们提供了使用这些疗法的试验的初步临床数据的概述,包括咬®(双特异性 T 细胞参与) 免疫肿瘤治疗 AMG 420,抗体-药物结合物 GSK2857916,以及几种 CAR T 细胞治疗剂,包括 bb2121,NIH CAR-BCMA 和 LCAR-B38M。在这些治疗方法中,已经观察到显著的抗叶细胞瘤活性和高的微小残留疾病阴性率。这些临床数据概述了 BCMA 靶向治疗改善 MM 治疗前景的潜力。重要的是,迄今为止的临床结果表明,这些疗法可能有希望产生深刻而持久的反应,并支持早期治疗路线的进一步研究,包括新诊断的 MM。

antigen

免疫 抗原 临床研究术语
概述  :  

抗原是指能够刺激机体产生(特异性)免疫应答,并能与免疫应答产物抗体和致敏淋巴细胞在体内外结合,发生免疫效应(特异性反应)的物质。并非所有外源或自身物质都可以成为抗原,具备免疫原性和免疫反应性两个重要特性的物质才是抗原。抗原诱导机体产生的适应性免疫应答仅对该抗原专一,而与其他抗原不反应,这种性质称为抗原的抗原特异性。 特性 抗原具备两个重要特性:免疫原性(immunogenicity)和免疫反应性(immunoreactivity)。免疫原

antigen    英 [’æntidʒən] 美 [’æntidʒən]

释    义    n.抗原

同根词    antibody n. 抗体

antivirus n. 反病毒程序;抗病毒素

antibiotic adj. 抗生的;抗菌的;n. 抗生素,抗菌素

例    句    The expressed protein as an antigen can be used to differentiate the infection from vaccination.作为抗原的表达蛋白可用于区分感染和疫苗接种。

请扫描右侧二维码,免费查看词汇专业知识背景