Self-Assembly of Epitope-Tagged Proteins and Antibodies for Delivering Biologics to Antigen Presenting Cells

Abstract

Inspired by the immune system's own strategy for macrophage activation, we describe here a simple self-assembly strategy for generating artificial immune complexes. The built-in recognition domains in the antibody, viz. the Fab and Fc domains, are judiciously leveraged for cargo conjugation to generate the nanoassembly and macrophage targeting, respectively. A responsive linker is engineered into the nanoassembly for releasing the protein cargo inside the macrophages, while ensuring stability during delivery. The design principles are simple and versatile to be applicable to a range of biologics, from small protein toxins to large enzymes, with high loading capacity. This self-assembly platform has the potential for delivering biologics to immune cells with implications in immunotherapy.