抗体靶向治疗在弥漫性大B细胞淋巴瘤中的研究进展

Progress in novel monoclonal antibodies in the treatment of diffuse large B-cell lymphoma

摘要:

弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）是一种侵袭性淋巴瘤，通常采用含CD20单克隆抗体（利妥昔单抗）的免疫化疗方案，然而仍有部分复发难治（relapsed/refractory，R/R）患者无法获得临床治愈。近年来，不少新开发的单抗类药物用于治疗DLBCL，显著改善了R/R DLBCL的预后。本综述系统讨论这些单抗类药物，包括传统简单结构的单克隆抗体、双特异性抗体（bispecific antibodies，bsAb）及抗体-药物偶联物（antibody-drug conjugates，ADCs）。首先介绍除利妥昔单抗以外的其他传统单抗，主要涉及单抗结构上的改进及针对更多的靶点。接着详细阐述bsAb的基本结构和作用机制，以及各种不同双抗结合位点带来的多种可能及尝试。最后对ADCs的作用机制及结构各部分做详细的分析比较。文中还介绍这些单抗类药物用于治疗DLBCL的最新临床试验数据，包括反应率、无进展生存期等疗效结果，以及主要的不良反应。

Abstract:

Diffuse large B-cell lymphoma（DLBCL） is an aggressive lymphoma usually treated with CD20 monoclonal antibodies （mAb），rituximab in combination with chemotherapy. However，there are still some relapsed/refractory（R/R） patients who cannot be cured. In recent years，many novel monoclonal antibodies have been developed to treat DLBCL，which has significantly improved the prognosis of R/R DLBCL. In this review，we systematically discuss these mAb，including traditional mAb，bispecific antibodies （bsAb），and antibody-drug conjugates（ADCs）. Firstly，other traditional mAb rather than rituximab are introduced in this review， mainly involving the improvement of monoclonal antibody structure and targeting more targets. Then，we elaborate the basic structure and mechanism of bsAb，as well as various possibilities brought by various combination from different binding sites. Finally，the mechanism and structure of ADCs are analyzed and compared in detail. The article also reviews the latest clinical trial data of these antibodies in treatment of DLBCL，including response rates，progression-free survival and other efficacy results，as well as major adverse reactions.