双特异性抗体治疗 B 细胞淋巴瘤:前景、未知与机遇
Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities.
机构信息
Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
出版信息
Blood. 2023 Feb 2;141(5):467-480. doi: 10.1182/blood.2021011994.
Treatment paradigms for B-cell non-Hodgkin lymphomas (B-NHL) have shifted dramatically in the last 2 decades following the introduction of highly active immunotherapies such as rituximab. Since then, the field has continued to witness tremendous progress with the introduction of newer, more potent immunotherapeutics, including chimeric antigen receptor T-cell therapy, which have received regulatory approval for and currently play a significant role in the treatment of these diseases. Bispecific antibodies (BsAb) are a novel class of off-the-shelf T-cell redirecting drugs and are among the most promising immunotherapeutics for lymphoma today. BsAb may target various cell-surface antigens and exist in different formats. Anti-CD20xCD3 BsAb have demonstrated remarkable single-agent activity in patients with heavily pretreated B-NHL with a manageable toxicity profile dominated by T-cell overactivation syndromes. Much work remains to be done to define the optimal setting in which to deploy these drugs for B-NHL treatment, their ideal combination partners, strategies to minimize toxicity, and, perhaps most importantly, pharmacodynamic biomarkers of response and resistance. In this review, we provide an update on BsAb development in B-NHL, from discovery to clinical applications, highlighting the achievements, limitations, and future directions of the field.
在引入利妥昔单抗等高度活跃的免疫疗法后,B 细胞非霍奇金淋巴瘤(B-NHL)的治疗模式在过去 20 年中发生了巨大变化。此后,随着新型、更有效的免疫疗法的引入,包括嵌合抗原受体 T 细胞疗法,该领域继续取得巨大进展,这些疗法已获得监管部门的批准,并在这些疾病的治疗中发挥着重要作用。双特异性抗体(BsAb)是一种新型的即用型 T 细胞重定向药物,是目前最有前途的淋巴瘤免疫疗法之一。BsAb 可以针对各种细胞表面抗原,并且存在不同的形式。抗 CD20xCD3 BsAb 在经过大量预处理的 B-NHL 患者中具有显著的单药活性,其毒性特征可管理,主要表现为 T 细胞过度激活综合征。在为 B-NHL 治疗确定使用这些药物的最佳方案、理想的联合伙伴、降低毒性的策略以及可能最重要的是反应和耐药的药效学生物标志物方面,仍有许多工作要做。在这篇综述中,我们从发现到临床应用,提供了 B-NHL 中 BsAb 开发的最新进展,强调了该领域的成就、局限性和未来方向。