A universal in silico V(D)J recombination strategy for developing humanized monoclonal antibodies.

ABSTRACT:

Background

Humanization of mouse monoclonal antibodies (mAbs) is crucial for reducing their immunogenicity in humans. However, humanized mAbs often lose their binding affinities. Therefore, an in silico humanization method that can prevent the loss of the binding affinity of mAbs is needed.

Methods

We developed an in silico V(D)J recombination platform in which we used V(D)J human germline gene sequences to design five humanized candidates of anti-tumor necrosis factor (TNF)-α mAbs (C1-C5) by using different human germline templates. The candidates were subjected to molecular dynamics simulation. In addition, the structural similarities of their complementarity-determining regions (CDRs) to those of original mouse mAbs were estimated to derive the weighted interatomic root m

SUBMITTER: Hsieh YC 

PROVIDER: S-EPMC8805405 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature