Di‐, tri‐ and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding

FEBS Letters

Little, Melvyn²  Kipriyanov, Sergey M.²  Le Gall, Fabrice²  Moldenhauer, Gerhard¹ 

[1] Department of Molecular Immunology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany;Recombinant Antibody Research Group (D0500), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany

关键词: Single chain Fv;    Diabody;    Triabody;    Tetrabody;    Human CD19;   

DOI  :  10.1016/S0014-5793(99)00713-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Single chain variable fragments (scFv) of the murine monoclonal antibody HD37 specific to human B-cell antigen CD19 were constructed by joining the V_H and V_L domains with linkers of 18, 10, 1 and 0 residues. ScFv-18 formed monomers, dimers and small amounts of tetramers; scFv-10 formed dimers and small amounts of tetramers; scFv-1 formed exclusively tetramers; scFv-0 formed exclusively trimers. The affinities of the scFv-10 (diabody) and scFv-1 (tetrabody) were approximately 1.5- and 2.5-fold higher, respectively, than that of the scFv-0 (triabody). The tetrabody displayed a significantly prolonged association with cell-bound antigen (t _1/2 cell surface retention at 37°C of 26.6 min) compared to both the diabody (13.3 min) and triabody (6.7 min). This increase in avidity of the tetrabody combined with its larger size could prove to be particularly advantageous for imaging and the immunotherapy of B-cell malignancies.

【 授权许可】

Unknown