Augmented Binary Substitution: Single-pass CDR germ-lining and stabilization of therapeutic antibodies.

ABSTRACT: Although humanized antibodies have been highly successful in the clinic, all current humanization techniques have potential limitations, such as: reliance on rodent hosts, immunogenicity due to high non-germ-line amino acid content, v-domain destabilization, expression and formulation issues. This study presents a technology that generates stable, soluble, ultrahumanized antibodies via single-step complementarity-determining region (CDR) germ-lining. For three antibodies from three separate key immune host species, binary substitution CDR cassettes were inserted into preferred human frameworks to form libraries in which only the parental or human germ-line destination residue was encoded at each position. The CDR-H3 in each case was also augmented with 1 ± 1 random substitution per clone.

SUBMITTER: Townsend S 

PROVIDER: S-EPMC4687607 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature