Engineering multi-specific nano-antibodies for cancer immunotherapy

Area of Science:

• Biotechnology
• Nanomedicine
• Immunology

Background:

• Multi-specific antibodies offer therapeutic advantages but are challenging to produce.
• Current methods for immobilizing monoclonal antibodies (mAbs) on nanoparticles face limitations in complexity, affinity, and biosecurity.
• Existing multi-specific nano-antibodies (multi-NanoAbs) have faced hurdles in clinical translation due to fabrication difficulties.

Purpose of the Study:

• To develop a versatile nano-adaptor for simplified and controlled immobilization of multiple mAbs.
• To construct multi-NanoAbs with enhanced affinity, biosecurity, and therapeutic efficacy.
• To demonstrate the potential for large-scale production and clinical translation of novel multi-NanoAbs.

Main Methods:

• Engineered a recombinant fusion protein comprising Fc gamma receptor 1 (FcγR1) and serum albumin, combined with poly(L-lactide).
• Utilized FcγR1-mAb receptor-ligand interactions for antibody immobilization, avoiding complex chemical conjugation.
• Constructed diverse multi-NanoAbs using the developed nano-adaptor system.

Main Results:

• The fusion protein/polymer-based nano-adaptor enabled convenient and controlled construction of multi-NanoAbs.
• Demonstrated efficacious therapeutic effects of the constructed multi-NanoAbs.
• Achieved large-scale production of the humanized nano-adaptor and confirmed anti-tumor effectiveness in mouse models.

Conclusions:

• The novel nano-adaptor system overcomes key limitations in multi-NanoAb development, including fabrication complexity and mAb affinity loss.
• The developed multi-NanoAbs show significant anti-tumor effectiveness, indicating strong potential for clinical applications.
• This approach facilitates the creation of advanced nanomedicines with improved therapeutic profiles and prospects for clinical translation.