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Di‐, tri‐ and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding
Author(s) -
Le Gall Fabrice,
Kipriyanov Sergey M.,
Moldenhauer Gerhard,
Little Melvyn
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00713-9
Subject(s) - chemistry , avidity , cd19 , antibody , microbiology and biotechnology , single chain variable fragment , antigen , monomer , monoclonal antibody , stereochemistry , cell , recombinant dna , biochemistry , biology , organic chemistry , gene , immunology , polymer , genetics
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.