单链抗体的制备及其在妇科肿瘤中的应用

doi:10.12280/gjfckx.20250823

摘要/Abstract

摘要：

单链抗体是一种基因工程抗体，仅由抗体的重链可变区和轻链可变区通过一段柔性连接肽连接而成，是具备完整抗原结合活性的最小抗体片段。相较于传统抗体，单链抗体具有分子质量小、组织穿透力强、免疫原性低及易于基因工程改造的显著优势。其制备核心在于利用噬菌体展示、核糖体展示等展示技术，从构建的文库中筛选出高亲和力与高特异性的单链抗体克隆，继而通过大肠杆菌、酵母或哺乳动物细胞等表达系统进行蛋白表达。目前研究主要聚焦于其在妇科肿瘤中的应用。在诊断方面，作为分子探针，单链可变片段（single-chain variable fragment，scFv）可与放射性核素偶联用于正电子发射体层成像，实现对肿瘤的精准定位与分期。在治疗方面，scFv功能高度多样化，既可充当“导弹头”精准递送干扰小RNA、毒素、化疗药物等治疗性分子，也能直接中和致癌因子，还可用于构建免疫毒素及靶向双特异性抗体，以协同抑制肿瘤生长并激活抗肿瘤免疫。此外，单链抗体卓越的组织穿透能力使其在治疗血供较差的实体瘤及腹膜转移灶方面展现出传统抗体难以比拟的优势。尽管前景广阔，但单链抗体的临床转化仍面临半衰期短、稳定性差及潜在免疫原性等挑战。未来，通过蛋白质工程优化其理化性质、开发新型递送系统以及拓展其在诊疗一体化中的应用，将是推动单链抗体在妇科肿瘤精准治疗中实现突破的关键。

关键词: 单链抗体, 生殖器肿瘤，女（雌）性, 诊断, 治疗, 制备

Abstract:

Single-chain antibodies are recombinant constructs comprising only the heavy- and light-chain variable domains tethered by a flexible peptide linker, representing the smallest intact antigen-binding fragment. Compared with full-length antibodies, single-chain antibodies exhibit lower molecular weight, superior tissue penetration, reduced immunogenicity, and facile genetic manipulation. High-affinity, high-specificity clones are routinely isolated from phage display, ribosome display, or alternative combinatorial libraries, followed by scalable production in Escherichia coli, yeast, or mammalian expression systems. Current translational research focuses on gynecologic tumors. For diagnostics, radionuclide-conjugated single-chain variable fragment (scFv) serves as molecular probes in positron emission tomography to enable accurate tumor localization and staging. Therapeutically, scFvs function as targeting moieties to deliver small interfering RNA, toxins, or chemotherapeutics, neutralize oncogenic ligands, or constitute recombinant immunotoxins and bispecific antibodies that simultaneously inhibit neoplastic growth and activate anti-tumor immunity. Their exceptional penetration confers unique advantages in poorly vascularized solid tumors and peritoneal metastatic deposits relative to conventional antibodies. Clinical transformation is nevertheless constrained by short serum half-life, limited stability, and potential immunogenicity. Future efforts directed toward protein-engineering optimisation, development of advanced delivery platforms, and theranostic integration will be pivotal for advancing precise management of gynecologic tumors.

Key words: Single-chain antibodies, Genital neoplasms, female, Diagnosis, Therapy, Preparation

王锦霞, 汪海燕, 祁亚玲, 刘洋, 刘会玲. 单链抗体的制备及其在妇科肿瘤中的应用[J]. 国际妇产科学杂志, 2026, 53(1): 1-7.

WANG Jin-xia, WANG Hai-yan, QI Ya-ling, LIU Yang, LIU Hui-ling. Generation and Gynecologic Tumor Applications of Single-Chain Antibodies[J]. Journal of International Obstetrics and Gynecology, 2026, 53(1): 1-7.

图/表 2

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