Institute of Neuropathology, University Medical Center, Georg August University, 37099, Göttingen, Germany.
Department of Neurology, University Medical Center, Georg August University, 37099, Göttingen, Germany.
Neurotherapeutics. 2021 Jul;18(3):1602-1622. doi: 10.1007/s13311-021-01048-z. Epub 2021 Apr 20.
Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS-namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20 cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性疾病，仍然是导致早期发病后持续残疾的最常见原因之一。越来越多的证据表明 B 细胞在其发病机制和进展中起着关键作用。在过去的几十年中，针对表面蛋白 CD20 的单克隆抗体（mab）已被作为复发型多发性硬化症（RMS）和原发性进行性多发性硬化症（PPMS）的 B 细胞靶向治疗进行了深入研究。RMS 中抗 CD20 治疗的关键研究表明了其具有显著的临床和影像学效果，特别是对急性炎症和复发生物学。这些结果为进一步研究 B 细胞在 MS 发病机制中的作用铺平了道路。除了控制 RMS 中的复发发展外，奥瑞珠单抗（OCR）在 PPMS 患者中也显示出临床益处，并成为该疾病过程的第一种批准药物。在这篇综述中，我们概述了目前用于治疗 MS 的抗 CD20 mab，即利妥昔单抗（RTX）、奥瑞珠单抗（OCR）、奥法妥木单抗（OFA）和乌利昔单抗（UB）。除了它们的有效性外，我们还讨论了可能的局限性和安全问题，特别是在长期治疗方面，包括该类药物的总体情况以及每种抗 CD20 mab 的个体情况。此外，我们阐明了抗 CD20 治疗在何种程度上可能改变其他免疫细胞的功能，无论是直接还是间接的。最后，我们涵盖了关于抗 CD20 治疗停止后 CD20 细胞再群集的现有知识，并讨论了针对替代、进一步开发的 B 细胞沉默治疗的未来愿望。
