Merck Bioventures, Discovery Biologics, Merck & Co., Inc., Rahway, NJ, USA.
MAbs. 2010 Jan-Feb;2(1):14-9. doi: 10.4161/mabs.2.1.10789. Epub 2010 Jan 30.
Approval of an anti-CD20 chimeric monoclonal antibody, rituximab, has revolutionized cancer treatment and also validated CD20 targeting for providing benefit and improvement of overall response rate in B cell malignancies. Although many patients have benefited from the treatment of rituximab, there are still significant numbers of patients who are refractory or develop resistance to the treatment. Here we discuss pre-clinically well-defined potential mechanisms of action for rituximab and review the ways next generation anti-CD20 monoclonal antibodies can potentially exploit them to further enhance the treatment of B cell malignancies. Although the relative importance of each of these mechanism remains to be established in the clinic, well-designed clinical trials will help to define the efficacy and understanding of which effector activity of modified next generation anti-CD20 mAb will be important in the treatment of B-cell malignancies.
批准抗 CD20 嵌合单克隆抗体利妥昔单抗彻底改变了癌症治疗方法，也验证了针对 CD20 的靶向治疗可带来获益，并提高 B 细胞恶性肿瘤的总体反应率。虽然许多患者从利妥昔单抗的治疗中受益，但仍有大量患者对此治疗有耐药性或产生抵抗性。在此，我们讨论了利妥昔单抗在临床前明确的潜在作用机制，并综述了下一代抗 CD20 单克隆抗体可能利用这些机制来进一步增强 B 细胞恶性肿瘤治疗的方法。虽然这些机制中的每一种在临床中的相对重要性仍有待确定，但精心设计的临床试验将有助于确定疗效，并了解改良下一代抗 CD20 mAb 的哪种效应子活性在 B 细胞恶性肿瘤的治疗中重要。
