Design of antibody variable fragments with reduced reactivity to preexisting anti-drug antibodies.

ABSTRACT: Upon reformatting of an antibody to single-chain variable fragment format, a region in the former variable/constant domain interface of the heavy chain becomes accessible for preexisting (PE) anti-drug antibody (ADA) binding. The region exposed because of this reformatting contains a previously hidden hydrophobic patch. In this study, mutations are introduced in this region to reduce PE ADA reactivity and concomitantly reduce the hydrophobic patch. To enhance our understanding of the importance of individual residues in this region with respect to PE ADA reactivity, a total of 50 molecules for each of two antibodies against different tumor-associated antigens were designed, produced, and characterized by an arsenal of biophysical methods. The aim was to identify suitable mutations that red

SUBMITTER: Johansson MU 

PROVIDER: S-EPMC10269415 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature