Department of Haematooncology, University Hospital Ostrava, 708 52 Ostrava, Czech Republic.
Faculty of Medicine, University of Ostrava, 708 52 Ostrava, Czech Republic.
Int J Mol Sci. 2021 Oct 25;22(21):11470. doi: 10.3390/ijms222111470.
Over the last few years, treatment principles have been changed towards more targeted therapy for many B-cell lymphoma subtypes and in chronic lymphocytic leukemia (CLL). Immunotherapeutic modalities, namely monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cell therapy, commonly use B-cell-associated antigens (CD19, CD20, CD22, and CD79b) as one of their targets. T-cell engagers (TCEs), a subclass of bsAbs, work on a similar mechanism as CAR-T cell therapy without the need of previous T-cell manipulation. Currently, several anti-CD20xCD3 TCEs have demonstrated promising efficacy across different lymphoma subtypes with slightly better outcomes in the indolent subset. Anti-CD19xCD3 TCEs are being developed as well but only blinatumomab has been evaluated in clinical trials yet. The results are not so impressive as those with anti-CD19 CAR-T cell therapy. Antibody-drug conjugates targeting different B-cell antigens (CD30, CD79b, CD19) seem to be effective in combination with mAbs, standard chemoimmunotherapy, or immune checkpoint inhibitors. Further investigation will show whether immunotherapy alone or in combinatory regimens has potential to replace chemotherapeutic agents from the first line treatment.
在过去的几年中，针对许多 B 细胞淋巴瘤亚型和慢性淋巴细胞白血病（CLL），治疗原则已经向更具针对性的治疗方法转变。免疫治疗方法，即单克隆抗体（mAbs）、双特异性抗体（bsAbs）、抗体药物偶联物（ADCs）和嵌合抗原受体 T（CAR-T）细胞疗法，通常将 B 细胞相关抗原（CD19、CD20、CD22 和 CD79b）作为其靶点之一。T 细胞衔接器（TCEs），是 bsAbs 的一个子类，其作用机制与 CAR-T 细胞疗法相似，但无需对 T 细胞进行预先操作。目前，几种抗 CD20xCD3 TCE 已在不同的淋巴瘤亚型中显示出有希望的疗效，在惰性亚组中效果略好。抗 CD19xCD3 TCE 也在开发中，但目前只有blinatumomab 在临床试验中进行了评估。结果并不像抗 CD19 CAR-T 细胞疗法那样令人印象深刻。针对不同 B 细胞抗原（CD30、CD79b、CD19）的抗体药物偶联物与 mAbs、标准化疗免疫疗法或免疫检查点抑制剂联合使用似乎有效。进一步的研究将表明，免疫疗法单独或联合治疗方案是否有可能替代一线治疗中的化疗药物。
