Modular Platform for Efficient Assembly of Multifunctional Antibodies Using Orthogonal Protein-Protein Interactions

ABSTRACT

Multifunctional antibodies, capable of simultaneously engaging multiple targets, are a unique class of antibodies that have sparked growing interest. Current approaches for making multifunctional antibodies, including chemical conjugation or genetic modifications, suffer from low product yield, complex structure design, and complicated manufacturing processes. In this study, we report a modular post-translational platform with highly specific protein-protein interactions for multifunctional antibody assembly and an elastin-like polypeptide (ELP) for easy purification. We generated and purified multifunctional antibodies with over 90% assembled scaffold and overall product purity. Additionally, we assembled antibodies with diverse applications, including detecting cancer, inhibiting cancer cell growth, and directing T cells to cancer cells for enhanced therapeutic efficacy. This platform offers high assembly efficiency, easy purification, and modularity for the redesign of antibody functions.