Department of Biomedical Sciences, University of Catania, Catania, Italy.
Front Biosci (Landmark Ed). 2011 Jan 1;16(2):770-82. doi: 10.2741/3719.
The addition of anti-CD20 monoclonal antibody (rituximab) to chemotherapy has significantly improved survival in B-cell lymphoma. However, a substantial number of patients relapse after treatment with rituximab. Understanding of anti-CD20 antibody molecular function may facilitate the development of pharmacologic strategies to overcome resistance. Cell death have been demonstrated to be caused by rituximab binding to CD20 throughout direct and indirect mechanisms. The direct mechanism comprises growth inhibition, induction of apoptosis and sensitization of cells to chemotherapy. While, the indirect mechanisms to Rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). However, these mechanisms are still poorly understood. To shed light on this issue, we have analyzed the most significant results showing the role of Rituximab as a signal-inducing antibody and as a chemosensitizing agent through negative regulation of major survival pathways. Mechanisms of resistance to Rituximab are also discussed. Additionally, studies here reported show that, cellular targets are modified after treatment with Rituximab and may become useful for novel therapeutic strategies in the treatment of patients resistant to standard therapy.
抗 CD20 单克隆抗体（利妥昔单抗）联合化疗显著改善了 B 细胞淋巴瘤患者的生存。然而，相当数量的患者在接受利妥昔单抗治疗后复发。对抗 CD20 抗体分子功能的了解可能有助于开发克服耐药性的药物策略。已证明细胞死亡是由利妥昔单抗通过直接和间接机制与 CD20 结合引起的。直接机制包括生长抑制、诱导细胞凋亡和增强细胞对化疗的敏感性。而间接机制包括补体依赖性细胞毒性（CDC）和抗体依赖性细胞毒性（ADCC）。然而，这些机制仍知之甚少。为了解决这个问题，我们分析了最重要的结果，这些结果表明利妥昔单抗作为信号诱导抗体和通过负向调节主要生存途径作为化疗增敏剂的作用。还讨论了对利妥昔单抗的耐药机制。此外，这里报道的研究表明，细胞靶标在利妥昔单抗治疗后发生修饰，这可能为治疗对标准治疗耐药的患者的新型治疗策略提供有用信息。
