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新型小分子抗体scFv多聚体与肿瘤靶向
New Type Recombinant Antibody Fragment scFv Multimer and Cancer Targeting
【摘要】 新型小分子抗体—单链可变区片段 (sc Fv)是由一弹性接头 (linker)将 VH和 VL 连接而成 ,是抗体具有抗原结合部位的最小功能结构单位。以分子量小、体内半衰期短、免疫原性低、可在原核细胞系统表达、易于基因工程操作等特点而倍受关注。依据接头的长度和 V区的方向 ,sc Fv分子可聚集形成二聚体 (Diabody)、三聚体 (tri-abody)和四聚体 (tetrabody)。我们就 sc Fv分子接头长度和 V区方向、sc Fv多聚体的表达和稳定性、sc Fv多聚体在体内的药代动力学、sc Fv多聚体的弹性和亲和力、鼠源性 sc Fv多聚体的体外应用、多特异性 Sc Fv多聚体与肿瘤靶向几个方面作一综述
【Abstract】 New type recombinant antibody single chain variable fragment (scFv) is formed by the joined V H and V L domains of immunoglobulin with the used of a polypeptide linker that is at least 12 residues in length. scFv is the smallest functional unit of antibody and has shown a fine prospect for the radioimmunoscintigraphy of cancer because of its special characteristics including increased tumour penetration and fast clearance rates compared with parent Ig. A scFv molecule with a linker of 3 12 residues cannot fold into a functional Fv domain and instead associates with a second scFv molecule to form a bivalent dimer (Diabody).Reducing the linker length below three residues can force scFv association into trimers (Triabody) or tetramers (Tetrabody) depending on linker length, composition and V domain orientation. This review describes linker length and V domain orientation of scFv, expression and stability of scFv multimers, size of scFv multimers and its effect on in vivo pharmacokinetics, flexibility and avidity of scFv multimers, in vitro application of multimeric murine scFv, multispecific scFv multimers and cancer targeting.
- 【文献出处】 生物医学工程学杂志 ,Journal of Biomedical Engineering , 编辑部邮箱 ,2003年02期
- 【分类号】R392
- 【被引频次】9
- 【下载频次】223