FcγR1-Expressing Cell Membrane-Coated Nanoparticle (FcγR1-CMNP) for T-Cell-Engaging Bispecific Nanoantibody Construction

Abstract

T-cell-engaging bispecific antibodies (BiTEs), which can simultaneously bind to antigens on tumor cells and T cells, show good potential in cancer immunotherapy. A practical and feasible approach for emulating BiTEs involves immobilizing two types of monoclonal antibodies (mAbs) onto a single nanoparticle; however, this approach involves complex immobilization processes and chemical reactions. To overcome these challenges, we achieved gentle antibody immobilization through receptor–ligand interactions by constructing a mAb delivery system known as Fcγ receptor 1 (FcγR1)-expressing cell membrane-coated nanoparticles (abbreviated as FcγR1-CMNPs). To validate the functionality and feasibility of this approach, we immobilized αCD3 and αCD20 onto the CMNP surface and generated a bispecific nanoantibody (termed CMNP@CD3 × CD20) for treating B-cell lymphoma. We demonstrated that CMNP@CD3 × CD20 significantly promoted the interaction between T cells and tumor cells and resulted in the potent killing of tumor cells in vitro and in vivo. This innovative antibody delivery system offers a straightforward and gentler technique for antibody delivery, potentially facilitating the development of trispecific or multispecific antibody-based immunotherapy.