Antibody humanization-the Influence of the antibody framework on the CDR-H3 loop ensemble in solution.

ABSTRACT: Antibody engineering of non-human antibodies has focused on reducing immunogenicity by humanization, being a major limitation in developing monoclonal antibodies. We analyzed four series of antibody binding fragments (Fabs) and a variable fragment (Fv) with structural information in different stages of humanization to investigate the influence of the framework, point mutations and specificity on the complementarity determining region (CDR)-H3 loop dynamics. We also studied a Fv without structural information of the anti-idiotypic antibody Ab2/3H6, because it completely lost its binding affinity upon superhumanization, as an example of a failed humanization. Enhanced sampling techniques in combination with molecular dynamics simulations allow to access micro- to milli-second timescales of t

SUBMITTER: Fernandez-Quintero ML 

PROVIDER: S-EPMC7098879 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature