抗CD22抗体治疗非霍奇金淋巴瘤探究进展.docVIP

抗CD22抗体治疗非霍奇金淋巴瘤探究进展 　 作者：路萍萍　孟志云　周明霞　王敏伟　窦桂芳 【摘要】 　　CD22抗原既是跨膜糖蛋白也是免疫球蛋白超家族的一员，限制性表达于成熟B细胞和大多数B细胞非霍奇金淋巴瘤(NHL)的表面，与B细胞的发展、分化和功能有着密切的关系。抗CD22抗原单克隆抗体被开发为NHL诊断和免疫治疗药物，其特点为减弱免疫源性和加强效应因子的相互作用。不同形式的抗CD22抗体作为单药或联合用药治疗NHL的Ⅰ/Ⅱ期临床试验显示，不同形式的抗CD22抗体对放疗化疗无效或复发的NHL病人临床效果良好，药代动力学呈剂量依赖线性关系，半衰期长，高效低毒，人体耐受良好，而且抗CD22抗体联合其他抗体治疗也取得令人鼓舞的结果。本文就CD22抗原的生理功能和作为NHL导向治疗靶分子的特点、抗CD22抗体在治疗中的类型及其与其他抗体的联合应用作了综述。 【关键词】 抗CD22抗体；epratuzumab；美罗华；非霍奇金淋巴瘤 　　Immunotherapy of Non-Hodgkin’s Lymphomas (NHL) by Anti-CD22 Antibody——Review 　　AbstractCD22 is a transmembrane sialoglycoprotein and a member of the immunoglobulin superfamily. Its expression is restricted to the B cell lineage and a vast majority of B cell NHLs. CD22 plays a key role in B cell development, survival, and function. Humanized anti-CD22 antibodies were developed to minimize the immunogenicity and to enhance effector interactions during their developments of diagnostic and immunotherapeutic agent. Preclinical test with anti-CD22 antibodies indicates that a single, conjugated or radiolabeled agent has shown preliminary antitumor activity in patients with recurrent and heavily pretreated NHL. Anti-CD22 antibodies were well tolerated, without dose-dependant toxicity. Anti-CD22 antibodies are currently being evaluated in combination with rituximab, and the early results suggest that the combination of the two antibodies are well tolerated and may result in better clinical activity than the single agent alone. Thus, anti-CD22 antibodies are theoretically good candidates alone and in combination with other drugs in the treatment of B cell malignancies. In this review, the physiologic function and characteristics of CD22 antigen as target molecule of guide therapy for NHL, the types of anti-CD22 antibodies in therapy of NHL and the combination use with other antibodies were summarized. 　　Key wordsanti-CD22 antibody; epratuzumab; rituximab; non-Hodgkin’s lymphoma 　　治愈血液恶性肿瘤是肿瘤学工作者多年来的一个梦想。在过去的几十年里其主要治疗方法为放疗和化疗，然而单克隆抗体治疗药物的开发为我们提供了新的治疗方案，可以使病人有效地