针对CD33分子的抗体偶联药物的研究进展

单克隆抗体因具有分子量小、毒副作用低、靶向性好等优点，近年来已成为肿瘤治疗用药的主要方式。CD33分子是免疫球蛋白超家族成员，同时也是唾液酸依赖的免疫球蛋白样凝集素家族的成员，在免疫调节过程中具有重要作用。CD33分子特异表达于白血病细胞表面而在造血干细胞中不表达，因而成为白血病免疫治疗的理想靶点。以CD33为靶点的抗体药物主要有CMA676、HUMl95、AVE9633、WM537LHIM3-4等，目前大多处于临床试验阶段。该实验室也在进行抗CD33全人源抗体的研究，利用噬菌体展示技术筛选与CD33胞外区特异性结合的单链抗体，并构建免疫毒素和抗体偶联药物以研究其体内外抗肿瘤作用。该文针对CD33分子及其抗体偶联药物的现状及趋势作一综述。

Progress in Antibody-Drug Conjugates Directed against CD33

Monoclonal antibody has become an important drug modality for the treatment of cancer, with the advantages of low molecular weight, low toxic effect and precise targeting. CD33 belongs to the immuno- globulin superfamily and is one of the sialic acid dependent IG-like lectin family, which plays an important role in the immune system. Most acute myelocytic leukemia （AML） cells, but not the surface of stem cells, have CD33 overexpression which makes the molecule an ideal target for AML therapy. Several antibody drugs directed against CD33 including CMA676, HUM195, AVE9633, WM53 and HIM3-4 have been reported. In our lab, a phage-dis- played human antibody library has been constructed and scFv antibodies specifically targeting against CD33 have been identified. On the basis of the scFv sequences, the specific immunotoxins have been developed and tested the cytotoxicity and anticancer activity in vitro and in vivo. This review focuses on the structure and function of CD33 and the development of antibody drues for CD33.