Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Curr Hematol Malig Rep. 2012 Mar;7(1):65-73. doi: 10.1007/s11899-011-0103-0.
CD33, a 67-kDa glycoprotein expressed on the majority of myeloid leukemia cells as well as on normal myeloid and monocytic precursors, has been an attractive target for monoclonal antibody (mAb)-based therapy of acute myeloid leukemia (AML). Lintuzumab, an unconjugated, humanized anti-CD33 mAb, has modest single-agent activity against AML but failed to improve patient outcomes in two randomized trials when combined with conventional chemotherapy. Gemtuzumab ozogamicin, an anti-CD33 mAb conjugated to the antitumor antibiotic calicheamicin, improved survival in a subset of AML patients when combined with standard chemotherapy, but safety concerns led to US marketing withdrawal. The activity of these agents confirms that CD33 remains a viable therapeutic target for AML. Strategies to improve the results of mAb-based therapies for AML include antibody engineering to enhance effector function, use of alternative drugs and chemical linkers to develop safer and more effective drug conjugates, and radioimmunotherapeutic approaches.
CD33 是一种 67kDa 的糖蛋白，在大多数髓系白血病细胞以及正常髓系和单核细胞前体上表达，是基于单克隆抗体 (mAb) 的急性髓系白血病 (AML) 治疗的一个有吸引力的靶点。Lintuzumab 是一种未缀合的人源化抗 CD33 mAb，对 AML 具有适度的单药活性，但在与常规化疗联合的两项随机试验中并未改善患者结局。吉妥珠单抗奥唑米星是一种与抗肿瘤抗生素卡利奇霉素偶联的抗 CD33 mAb，与标准化疗联合使用可改善部分 AML 患者的生存，但安全性问题导致该药在美国市场撤出。这些药物的活性证实 CD33 仍然是 AML 的可行治疗靶点。为改善基于 mAb 的 AML 治疗结果而采用的策略包括抗体工程以增强效应功能、使用替代药物和化学连接子来开发更安全有效的药物偶联物，以及放射免疫治疗方法。
