Synthesis of Bispecific Antibody Conjugates Using Functionalized Poly-ADP-ribose Polymers

Poly-ADP-ribose (PAR) is a natural type of polymer derived from enzymatic reactions catalyzed by cellular poly(ADP-ribose) polymerases (PARPs). Given its notable solubility and biocompatibility, the PAR polymer may function as effective carriers for therapeutics in addition to modulating biomolecular interactions in cells. To explore its therapeutic potential, we herein developed a PAR polymer-based bispecific antibody targeting both human epidermal growth factor receptor 2 (HER2) and T-cell CD3 antigens. This was accomplished by conjugating anti-HER2 and anti-CD3 monoclonal antibodies to azido-functionalized PAR polymers through click chemistry. The generated PAR polymer- anti-HER2/anti-CD3 antibody conjugate could not only bind specifically to both HER2-and CD3-expressing target cells but also display potent cytotoxicity against HER2-positive breast cancer cells in the presence of non-activated human peripheral blood mononuclear cells (PBMCs). Functionalized PAR polymers provide a new strategy for synthesizing bispecific antibodies and may enable generation of PAR polymer-based conjugates with unique pharmacological activities for biomedical applications.

Automated summary

In this study, a PAR polymer-based bispecific antibody targeting both HER2 and T-cell CD3 antigens was developed. The conjugate had specific binding to target cells expressing HER2 and CD3, and exhibited potent cytotoxicity against HER2-positive breast cancer cells in the presence of non-activated PBMCs. Functionalized PAR polymers provide a new strategy for synthesizing bispecific antibodies with unique pharmacological activities for biomedical applications.