Antigen binding and stability properties of non-covalently linked anti-CD22 single-chain Fv dimers

Antigen binding and stability properties of non-covalently linked anti-CD22 single-chain Fv dimers
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DOI:
10.1016/j.febslet.2004.11.011
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发表时间:
2004-12-17
期刊:
影响因子:
3.5
通讯作者:
Rybak, SM
Rybak, SM
中科院分区:
生物学3区
文献类型:
--
作者:
Arndt, MAE;Krauss, R;Rybak, SM

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通过改变接头长度和结构域取向,产生单价抗CD 22单链片段可变(scFv)抗体的三种多价衍生物。将V-H-V-L取向的scFv的接头缩短至5或0个残基分别导致双抗体或四聚体和三聚体的混合物的形成。出乎意料的是,当在37 ℃下在人血清中孵育时,组装成均质二聚体的V-L-0-V-H scFv保持比V-H-5-V-L双抗体基本上更稳定,并且当浓缩至4 mg/ml时保持其二聚体状态。这些性质表明V-L-0-V-H scFv可以成为一种有吸引力的载体,用于将多种效应分子选择性递送至CD 22(+)肿瘤细胞。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
By varying linker length and domain orientation three multivalent derivatives of a monovalent anti-CD22 single-chain fragment variable (scFv) antibody were generated. Shortening the linker of the V-H-V-L oriented scFv to 5 or 0 residues resulted in the formation of diabodies or a mixture of tetramers and trimers, respectively. Unexpectedly, a V-L-0-V-H scFv assembled to homogenous dimers, remained substantially more stable than the V-H-5-V-L diabody when incubated in human serum at 37 degreesC, and retained its dimeric state when concentrated up to 4 mg/ml. These properties suggest the V-L-0-V-H scFv could become an attractive vehicle for the selective delivery of multiple effector molecules to CD22(+) tumor cells. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.