Development of a potent high-affinity human therapeutic antibody via novel application of recombination signal sequence-based affinity maturation.

ABSTRACT: Therapeutic antibody development requires discovery of an antibody molecule with desired specificities and drug-like properties. For toxicological studies, a therapeutic antibody must bind the ortholog antigen with a similar affinity to the human target to enable relevant dosing regimens, and antibodies falling short of this affinity design goal may not progress as therapeutic leads. Herein, we report the novel use of mammalian recombination signal sequence (RSS)-directed recombination for complementarity-determining region-targeted protein engineering combined with mammalian display to close the species affinity gap of human interleukin (IL)-13 antibody 731. This fully human antibody has not progressed as a therapeutic in part because of a 400-fold species affinity gap. Using this nonhypo

SUBMITTER: Kielczewska A 

PROVIDER: S-EPMC8808179 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature