Engineering multi-specific nano-antibodies for cancer immunotherapy

Abstract

Immobilizing multiple types of monoclonal antibody (mAb) on nanoparticle surfaces is a promising approach for creating nanomedicines that emulate the functionality of multi-specific antibodies. However, the clinical translation of these multi-specific nano-antibodies (multi-NanoAbs) has been hindered by intricate fabrication procedures, inevitable attenuation in mAb affinity and insufficient carrier biosecurity. Here we develop a versatile nano-adaptor for immobilizing mAbs and construct multi-NanoAbs using a recombinant fusion protein that consists of Fc gamma receptor 1 and serum albumin, along with the biomedical polymer poly(l-lactide). Our findings demonstrate that fusion protein/polymer-based nano-adaptor is facilitated by FcγR1 on its surface to bind mAbs through receptor–ligand interactions rather than complex chemical conjugation and enables convenient and controlled construction of diverse multi-NanoAbs with efficacious therapeutic effects. We achieved large-scale production of humanized fusion protein/polymer-based nano-adaptor and confirmed the antitumour effectiveness of multi-NanoAb in humanized immune system mouse models, highlighting their prospects for clinical translation.