Facile generation of biepitopic antibodies with intrinsic agonism for activating tumor necrosis factor receptors.

ABSTRACT: Agonist antibodies are being pursued for therapeutic applications ranging from neurodegenerative diseases to cancer. For the tumor necrosis factor (TNF) receptor superfamily, higher-order clustering of three or more receptors is key to their activation, which can be achieved using antibodies that recognize two unique epitopes. However, the generation of biepitopic (i.e., biparatopic) antibodies typically requires animal immunization and is laborious and unpredictable. Here, we report a simple method for identifying biepitopic antibodies that potently activate TNF receptors without the need for additional animal immunization. Our approach uses existing, receptor-specific IgGs, which lack intrinsic agonist activity, to block their corresponding epitopes, then selects single-chain antibodies

SUBMITTER: Jhajj HS 

PROVIDER: S-EPMC11142405 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature