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作 者:Mingkai Wang Tianlei Ying Yanling Wu
机构地区:[1]MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology,School of Basic Medical Sciences,Department of Pulmonary and Critical Care Medicine,Department of Liver Surgery and Transplantation,Zhongshan Hospital,Fudan University,Shanghai 200032,China [2]Shanghai Engineering Research Center for Synthetic Immunology,Shanghai 200032,China
出 处:《Acta Pharmaceutica Sinica B》2024年第7期2854-2868,共15页药学学报(英文版)
基 金:supported by grants from the National Key R&D Program of China(2019YFA0904400);National Natural Science Foundation of China(32270984);Science and Technology Commission of Shanghai Municipality(23XD1400800,China);Shanghai Municipal Health Commission(GWVI-11.2-YQ46,China).
摘 要:Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic antibodies.These sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue penetration.However,the inherent challenges associated with the animal origin of sdAbs limit their clinical use.In recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their compatibility.This review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization methodologies.In addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.
关 键 词:Single-domain antibody NANOBODY HUMANIZATION Fully human singledomain antibody Solid tumor
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