Chemically generated IgG2 bispecific antibodies through disulfide bridging

Area of Science:

• Biotechnology
• Immunotherapy
• Protein Engineering

Background:

• Bispecific antibodies (BsAbs) offer expanded therapeutic potential by targeting multiple antigens or cell types simultaneously.
• Existing recombinant BsAb formats often present challenges in expression and purification.
• There is a need for simplified and efficient methods for generating functional BsAbs.

Purpose of the Study:

• To develop a novel chemical strategy for producing bispecific antibodies (BsAbs) utilizing native IgG2 architecture.
• To demonstrate the feasibility of generating a functional BsAb with retained antigen-binding potency.
• To overcome the challenges associated with recombinant BsAb expression and purification.

Main Methods:

• A chemical conjugation strategy was employed using native IgG2 antibody architecture.
• Full-length antibodies were chemically linked via disulfide bridges using orthogonal functional groups.
• An anti-HER2/EGFR bispecific antibody was generated using this novel chemical approach.

Main Results:

• The chemical conjugation strategy successfully produced a bispecific antibody (BsAb).
• The generated αHER2/EGFR BsAb demonstrated the ability to bind both target antigens.
• No significant loss of antigen-binding potency was observed in the produced BsAb.

Conclusions:

• The developed chemical strategy provides an effective method for generating bispecific antibodies (BsAbs) with native IgG2 architecture.
• This approach simplifies BsAb production compared to traditional recombinant methods.
• The retained potency of the generated αHER2/EGFR BsAb highlights the therapeutic potential of this method.