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.
