Institute of Basic Medical Sciences, Beijing, China.
Cancer Lett. 2010 Aug 1;294(1):66-73. doi: 10.1016/j.canlet.2010.01.023. Epub 2010 Mar 3.
Rituximab is the first anti-cancer antibody approved by the FDA for the treatment of B-cell lymphoma. However, its efficacy remains variable and often modest. Some patients are initially unresponsive to rituximab or later develop resistance to it, and require alternative therapies. Rituximab activity has been thought to involve antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and apoptosis. Present studies suggest that the patients unresponsive to rituximab may be helped with other CD20 antibodies with enhanced activities. In this study, we characterized a novel anti-CD20 chimeric antibody, TGLA, which binds to various B-cell lines specially and shares an epitope with rituximab. TGLA shows equal activities with rituximab, such as CDC, cell growth arrest and so on. Interestingly, TGLA also shows significant ADCC activity. Immunotherapeutic studies further show that TGLA is far more effective in delaying tumor growth than rituximab. These findings suggest that the ADCC-enhanced anti-CD20 antibody TGLA might be an alternative therapeutic agent for B-cell lymphoma.
利妥昔单抗是 FDA 批准的第一个用于治疗 B 细胞淋巴瘤的抗癌抗体。然而,其疗效仍然存在差异,通常效果有限。一些患者最初对利妥昔单抗无反应,或后来对其产生耐药性,需要替代疗法。利妥昔单抗的作用机制被认为涉及抗体依赖性细胞毒性(ADCC)、补体依赖性细胞毒性(CDC)和细胞凋亡。目前的研究表明,对利妥昔单抗无反应的患者可能会受益于其他具有增强活性的 CD20 抗体。在这项研究中,我们鉴定了一种新型的抗 CD20 嵌合抗体 TGLA,它能特异性地与各种 B 细胞系结合,并与利妥昔单抗共享一个表位。TGLA 与利妥昔单抗具有同等的活性,如 CDC、细胞生长抑制等。有趣的是,TGLA 还具有显著的 ADCC 活性。免疫治疗研究进一步表明,TGLA 在延缓肿瘤生长方面比利妥昔单抗更有效。这些发现表明,ADCC 增强的抗 CD20 抗体 TGLA 可能是治疗 B 细胞淋巴瘤的一种替代治疗药物。