Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma. Approximately 60% of patients are cured with R-CHOP as a frontline treatment, while the remaining patients experience primary refractory or relapsed disease (R/R). The prognosis for R/R DLBCL patients who are neither eligible for autologous stem-cell transplantations nor CAR-T-cell treatment is poor, representing an important unmet need. Monoclonal antibodies (mAbs) have dramatically improved therapeutic options in anti-cancer strategies, offering new opportunities to overcome chemo-refractoriness in this challenging disease, even in cases of primary non-responder DLBCL. Several novel mAbs, characterized by different mechanisms of action and targets, are now available for R/R DLBCL. Unbound mAbs induce an immune response against cancer cells, triggering different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), activation of antibody-dependent cell-mediated phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). Antibody–drug conjugates (ADCs) and radioimmunotherapy (RIT), respectively, deliver a cytotoxic payload or a beta-emitter radionuclide to the targeted cells and nearby bystanders. Bispecific T-cell engagers (BiTes) and immune checkpoint inhibitors (ICIs) redirect and enhance the immune response against tumor cells. Here, we review therapeutic strategies based on monoclonal antibodies for R/R DLBCL.
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的侵袭性淋巴瘤。约60%的患者通过一线R-CHOP方案治疗获得临床治愈，其余患者则出现原发难治或复发（R/R）。对于既不符合自体干细胞移植条件也无法接受CAR-T细胞治疗的R/R DLBCL患者，其预后较差，这构成了当前重要的未满足临床需求。单克隆抗体（mAbs）显著拓展了抗癌治疗策略的选择，为克服这类挑战性疾病的化疗耐药性提供了新机遇，甚至对原发无应答的DLBCL病例也展现出潜力。目前已有多种作用机制和靶点各异的新型单克隆抗体可用于治疗R/R DLBCL。游离态单抗通过诱导针对癌细胞的免疫反应，触发包括抗体依赖性细胞介导的细胞毒性（ADCC）、激活抗体依赖性细胞介导的吞噬作用（ADCP）以及补体依赖性细胞毒性（CDC）在内的多种作用机制。抗体药物偶联物（ADCs）和放射免疫疗法（RIT）则分别将细胞毒性载荷或β发射体放射性核素递送至靶细胞及其邻近区域。双特异性T细胞衔接器（BiTes）和免疫检查点抑制剂（ICIs）能够重定向并增强针对肿瘤细胞的免疫应答。本文系统综述基于单克隆抗体的R/R DLBCL治疗策略。
New Frontiers in Monoclonal Antibodies for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
肿瘤(癌症)患者之家