Immune silencing with targeted TGFb surrogate agonists

Stanford researchers have developed recombinant polypeptides targeting growth factor beta (TGF-?) receptor 1 and TGF? receptor 2 conjugated to a targeting moiety that binds to various target immune cells to induce suppression and silencing of target immune cells which may be useful for therapeutic applications.

Transforming growth factor beta (TGF-?) is a cytokine important in the maturation and differentiation of different lymphocytes. TGF-? binding to TGF-? receptor can lower proliferation and suppression of immune cells. However, TGF-? is toxic at high doses and does not have drug-like properties, limiting its potential clinical use in the suppression of immune cells and treatment of diseases.

To address these issues, the inventors developed TGF-? receptor agonists conjugated to antibodies for cell-specific targeting. In vitro and in vivo experiments have been conducted and show these conjugates are capable of independently and specifically silencing B cells, T cells, and all immune cells. These TGF-? agonist-antibody conjugates establishes a completely new immunotherapy modality that allows for selective inhibition of different immune cells without depletion.