CUE-401

CUE-401 is a first-in-class, preclinical bispecific fusion protein designed to induce and expand regulatory T cells (Tregs) in vivo by delivering two key immunomodulatory cytokine signals—modified transforming growth factor beta (TGF-β) and engineered interleukin 2 (IL-2)—simultaneously to the same target T cell. The molecule integrates a masked TGF-β with an attenuated IL-2 fused to an antibody Fc fragment, enabling “conditional binding” that avoids off-target activity and simplifies manufacturing. This dual-signal approach acts as a “master switch,” converting autoreactive effector T cells into stable, induced regulatory T cells (iTregs), establishing a tolerance-positive feedback loop that both increases nonspecific Treg populations and converts disease-causing autoreactive T cells into iTregs. Preclinical data demonstrate suppression of autoimmune responses in models of lupus, inflammatory bowel disease, rheumatoid arthritis, graft-versus-host disease, and transplant rejection. Developed by Cue Biopharma using its Immuno-STAT platform, CUE-401 aims to provide durable immune rebalance for multiple chronic autoimmune diseases[1][2][3][5][7][8].