美罗他格——CD33单抗偶联物治疗急性髓细胞白血病

Mylotarg——a new drug in treatment of acute myeloid leukemia.

CD33抗原大量表达于急性髓细胞白血病(AML)细胞表面,可成为靶向免疫治疗的目标。美罗他格是人源化抗CD33单克隆抗体与强效抗肿瘤抗生素——乙酰棘孢霉素偶联物,与髓性白血病细胞表面CD33抗原结合,进入细胞后释放棘孢霉素,对髓细胞白血病细胞有明显杀灭作用,用于治疗复发、难治的CD33+AML,获得良好疗效,与其它化疗药物联合应用治疗AML的临床试验正在进行中。美罗他格的耐受性一般较好,但肝脏毒性及肝静脉阻塞综合征等毒副反应值得关注。美罗他格的耐药机制可能来自多方面,其中包括P-糖蛋白介导的药物排出等。

CD33 antigen is highly expressed on the surface of acute myeloid leukemic blast cells, which becomes the target of immunotherapy. Mylotarg consists of a recombinant humanized immunoglobulin G4 （ lgG4 ） anti-CD33 monoclonal antibody and an antitumor antibiotic-N-acetyl-γ1-calicheamicin dimethyl hydrazide. Mylotarg binds to CD33 antigen on the surface of CD33 positive acute myeloid leukemic blast cells and after internalization, releases a cytotoxic drug-calicheamicin which has strong activity to kill myeloid leukemic blast cells. Administration of Mylotarg to patients with relapsed or refractory CD33-positive AML appears to be a fa- vorable profile. Chinical trials of combination of Mylotarg and chemotherapy for treatment of AML are underway. Mylotarg is usually well tolerated in adults with acute myeloid leukemia（ AML）, while some severe adverse effects such as hepatotoxicity including hepatic veno-occlusive disease occurred. Resistance to Mylotarg is likely mediated by multiple mechanisms including permeability glycoprotein-mediated drug efflux and so on.