单域抗体的特性及其临床开发进展  

Characteristics and clinical development status of therapeutic single domain antibody (sdAb)

作　　者：陈哲浩 李林鸿 曹王丽 金朱明 方玲 杨军[3,4] 王如伟 尚云龙 CHEN Zhe-hao;LI Lin-hong;CAO Wang-li;JIN Zhu-ming;FANG Ling;YANG Jun;WANG Ru-wei;SHANG Yun-long(Hangzhou Biolocon Bio-Tech Co.,Ltd.,Hangzhou 310051,China;Zhejiang CONBA Pharmaceutical Co.,Ltd.,Hangzhou 310051,China;Hangzhou Normal University School of Medicine,Hangzhou 310016,China;Zhejiang Provincial Center for Uterine Cancer Diagnosis and Therapy Research,Hangzhou 310006,China)

机构地区：[1]杭州贝罗康生物技术有限公司,杭州310051 [2]浙江康恩贝制药股份有限公司,杭州310051 [3]杭州师范大学医学院,杭州310016 [4]浙江省子宫恶性肿瘤诊治技术研究中心,杭州310006

出　　处：《中国新药杂志》2019年第21期2581-2587,共7页Chinese Journal of New Drugs

摘　　要：单域抗体是指一类在骆驼科动物体内发现的天然缺失抗体轻链和重链恒定区的重链抗体。通过免疫骆驼科动物或噬菌体展示技术,可以筛选得到针对特定抗原的特异性单域抗体。单域抗体不但具备常规单抗所具有的特异抗原识别能力,并且因其分子尺度小、结构简单而具备很多独特的优点及用途,但也因此在体内易被快速清除,半衰期短。目前在研的治疗类单域抗体往往采用多特异性分子联结、结构修饰或者融合蛋白的设计策略来延长体内半衰期,拓展特异性。本文重点对治疗类单域抗体的结构特点、应用优势及其作为新型抗体药物在国内外临床开发进展进行综述,并对其应用开发前景进行展望。Single domain antibody(sdAb),which naturally lacks the light chain and the constant regions of heavy chain,is a class of heavy chain antibodies found in Camelidae animals. Specific sd Abs can be expressed and screened by immunization of Camelidae animals or phage display technology. In addition to specific antigenbinding ability just as monoclonal antibody,sdAb also has many other unique advantages and applications due to its simple structure with small size,making it easy to be cleared in vivo,thus has a short half-life. The development of therapeutic sdAbs often take adventage of multi-specific molecular conjugation,structural modification or fusion protein design strategies to prolong the half-life in vivo and improve the specificity. This review focuses on the structural properties,advantages,and clinical development status of sdAb,and the prospect of sdAb as a novel therapeutic antibody drug was also discussed.

关 键 词：单域抗体 纳米抗体 重链抗体重链可变区 单域抗体偶联 半衰期 

分 类 号：R95[医药卫生—药学]