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

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 lightchain)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。

Abstract:

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.