Mechanistic modeling of a human IgG₄ monoclonal antibody (tralokinumab) Fab-arm exchange with endogenous IgG₄ in healthy volunteers.

ABSTRACT: Therapeutic IgG₄ antibodies engage in Fab-arm exchange with endogenous human immunoglobulin G4 (IgG₄ ) to form monovalent hybrid molecules. A mechanistic population model was developed to quantitatively characterize the dynamic Fab-arm exchange of tralokinumab, a human IgG₄  monoclonal antibody currently being developed for the treatment of atopic dermatitis, with endogenous IgG₄ in healthy volunteers. The estimated pharmacokinetic parameters for IgG₄ were similar to those of immunoglobulin G1 or immunoglobulin G2 in humans. However, the mechanistically modeled clearance of half molecules is 21-fold higher, likely due to the loss of avidity for the neonatal Fc receptor. Half molecules of tralokinumab randomly associate with those of en

SUBMITTER: Wang B 

PROVIDER: S-EPMC9007600 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature