Conversion of an agonistic anti-TNFR2 biparatopic antibody into an antagonist by insertion of peptide linkers into the hinge region.

ABSTRACT: Biparatopic antibodies (BpAbs) bind two different antigen epitopes to form characteristic immunocomplexes. Many BpAbs have been developed for enhanced crosslinking to induce signal transduction or cell internalization, whereas few have been reported with smaller immunocomplexes to suppress unwanted signaling. Here, we developed a strategy to induce 1:1 immunocomplex formation to maximize antagonistic function. Various peptide linkers were introduced into the hinge regions of IgG-like agonist BpAbs against tumor necrosis factor receptor 2. Loss of crosslinking activity was observed for one BpAb, allowing the conversion of its function from an agonist to an antagonist. However, crosslinking activity was retained for another agonist, BpAb, which binds to a different epitope pair. In a combine

SUBMITTER: Otsuki T 

PROVIDER: S-EPMC12452656 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature