Optimizing colloidal stability and viscosity of multispecific antibodies at the drug discovery-development interface: a systematic predictive case study.

ABSTRACT: The discovery and development of multispecific antibodies present unique challenges in optimizing their physicochemical properties to enhance developability and manufacturability. Common developability challenges include increased risk of aggregation, high viscosity, poor solubility, low expression yields, complex purification requirements, greater propensity for fragmentation, immunogenicity, or pharmacokinetics. In this study, we systematically investigate the solution behavior of engineered bispecific IgG1-VHH constructs derived from a parental NKp30 ×EGFR natural killer cell engager (NKCE) molecule, focusing on colloidal stability, hydrophobicity, thermal stability, pH sensitivity, and viscosity. By combining in silico predictions and experimental evaluations, we engineered vari

SUBMITTER: Siegmund V 

PROVIDER: S-EPMC12407640 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature