Adalimumab‐Poloxamer Conjugate for Bio‐Better: Enhanced Stability and Function

Abstract Polymer conjugation is applied to drugs, peptides, and proteins to enhance stability and impart functionalities. In the case of antibodies, polymers are often used as spacers or linkers in antibody‐drug conjugates to mitigate excessive hydrophobicity or increase the drug‐antibody ratio. However, the relatively large molecular weight and inherent stability of antibodies have limited expectations for polymer conjugation to further enhance their stability. In this study, antibody‐polymer conjugates (APCs) are fabricated to evaluate changes in the physicochemical stability of antibodies. Biocompatible polymers frequently used in clinical applications, polyethylene glycol and poloxamer (PX), are selected. Both polymers are confirmed to preserve the structural integrity of the conjugated antibodies, and this work aims to elucidate their influence on various antibody properties. APCs demonstrate significantly improved stability under various conditions compared to native antibodies. Furthermore, polymer conjugation is found to enhance affinity, with PX conjugates exhibiting improvements in both association and dissociation constants. These functional enhancements translate into increased antigen neutralization efficacy at the cellular level and extend therapeutic durations in animal models. This study presents polymer conjugation as a refined approach for optimizing antibodies. It highlights the potential of this strategy to enhance antibody efficacy without the need for additional drug conjugation.