Profiling the Biophysical Developability Properties of Common IgG1 Fc Effector Silencing Variants.

ABSTRACT: Therapeutic antibodies represent the most significant modality in biologics, with around 150 approved drugs on the market. In addition to specific target binding mediated by the variable fragments (Fvs) of the heavy and light chains, antibodies possess effector functions through binding of the constant region (Fc) to Fcγ receptors (FcγR), which allow immune cells to attack and kill target cells using a variety of mechanisms. However, for some applications, including T-cell-engaging bispecifics, this effector function is typically undesired. Mutations within the lower hinge and the second constant domain (CH2) of IgG1 that comprise the FcγR binding interface reduce or eliminate effector function ("Fc silencing") while retaining binding to the neonatal Fc receptor (FcRn), important for norma

SUBMITTER: Pejchal R 

PROVIDER: S-EPMC10526015 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature