Generic approach for the generation of stable humanized single-chain Fv fragments from rabbit monoclonal antibodies.

ABSTRACT: Despite their favorable pharmacokinetic properties, single-chain Fv antibody fragments (scFvs) are not commonly used as therapeutics, mainly due to generally low stabilities and poor production yields. In this work, we describe the identification and optimization of a human scFv scaffold, termed FW1.4, which is suitable for humanization and stabilization of a broad variety of rabbit antibody variable domains. A motif consisting of five structurally relevant framework residues that are highly conserved in rabbit variable domains was introduced into FW1.4 to generate a generically applicable scFv scaffold, termed FW1.4gen. Grafting of complementarity determining regions (CDRs) from 15 different rabbit monoclonal antibodies onto FW1.4 and their derivatives resulted in humanized scFvs with bin

SUBMITTER: Borras L 

PROVIDER: S-EPMC2838326 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature