噬菌体抗体库技术在肿瘤治疗中的研究进展及应用  

Phage antibody library technology in tumor therapy:a review

作　　者：陈晓阳 安瑞珩 黄菊 梁有沣 张文静 郝明炫 郭蕊 李小宁 李永超 应璐 杨昭 CHEN Xiaoyang;AN Ruiheng;HUANG Ju;LIANG Youfeng;ZHANG Wenjing;HAO Mingxuan;GUO Rui;LI Xiaoning;LI Yongchao;YING Lu;YANG Zhao(Innovation Center of Molecular Diagnostics,College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029,China;Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin of Xinjiang Production and Construction Corps,College of Life Science and Technology,Tarim University,Alar 843300,Xinjiang,China)

机构地区：[1]北京化工大学生命科学与技术学院分子诊断技术创新研究中心,北京100029 [2]塔里木大学生命科学与技术学院、新疆生产建设兵团塔里木盆地生物资源保护利用重点实验室,新疆阿拉尔843300

出　　处：《生物工程学报》2023年第9期3644-3669,共26页Chinese Journal of Biotechnology

基　　金：新疆科协青年人才托举工程项目(2021);北京化工大学-中日友好医院生物医学转化工程研究中心联合基金项目(XK2023-21);新疆生产建设兵团重点领域科技攻关计划项目(2022AB022)。

摘　　要：肿瘤是严重威胁人类健康的疾病。目前肿瘤治疗策略以手术切除、放化疗、靶向治疗和免疫治疗为主。单克隆抗体药物因具备高效性和低毒性等特点,逐渐成为肿瘤临床治疗中不可或缺的药物类型。噬菌体抗体库技术(phage antibody library technology,PALT)是一种新型的单克隆抗体制备技术,其将免疫球蛋白可变区VH(variable region of heavy chain)/VL(variable region of light chain)基因重组后整合在噬菌体载体上,并以融合蛋白的形式将抗体表达到噬菌体表面,从而获得多样性抗体库。抗体库经过“吸附-洗脱-扩增”过程即可筛选获得到特异结合抗原的抗体分子及其基因序列。PALT具有抗体生产周期短、抗体结构可塑性强、抗体产量大、多样性高和可直接生产人源化抗体等优点,已应用于乳腺癌、胃癌、肺癌和肝癌等肿瘤标志物的筛选和抗体药物的制备等领域。文中综述了PALT在肿瘤治疗中的研究进展及应用。Tumor is a serious threat to human health.At present,surgical resection,chemoradiotherapy,targeted therapy and immunotherapy are the main therapeutic strategies.Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity.Phage antibody library technology(PALT)is a novel monoclonal antibody preparation technique.The recombinant immunoglobulin variable region of heavy chain(VH)/variable region of light chain(VL)gene is integrated into the phage vector,and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library.Through the process of adsorption-elution-amplification,the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence.PALT has the advantages of short antibody production cycle,strong plasticity of antibody structure,large antibody yield,high diversity and direct production of humanized antibodies.It has been used in screening tumor markers and preparation of antibody drugs for breast cancer,gastric cancer,lung cancer and liver cancer.This article reviews the recent progress and the application of PALT in tumor therapy.

关 键 词：肿瘤 噬菌体抗体库技术 单克隆抗体 靶向治疗 标志物 

分 类 号：R73-36[医药卫生—肿瘤]