Transforming growth factor beta receptor type II-Interleukin-12 receptor fusion protein (TGFBR2-IL12R)

The Transforming growth factor beta receptor type II-Interleukin-12 receptor fusion protein, commonly referred to as the CTBR12 "TGF-β flip" receptor, is a synthetic chimeric protein designed to reprogram immune cell responses within the immunosuppressive tumor microenvironment [1]. It consists of the extracellular ligand-binding domain of the Transforming growth factor beta receptor type II (TGFBR2) fused to the intracellular signaling domains of the Interleukin-12 (IL-12) receptor [1, 2]. In many solid tumors, TGF-β is secreted at high levels to inhibit the activity of Natural Killer (NK) cells and T cells, facilitating immune evasion [3]. This engineered receptor subverts this mechanism by converting the inhibitory TGF-β signal into a stimulatory IL-12-like signal, which activates the STAT4 pathway and enhances the production of pro-inflammatory cytokines like interferon-gamma [1, 4]. This technology is a core component of next-generation adoptive cell therapies, such as Century Therapeutics' CNTY-102, which utilizes iPSC-derived NK cells to target refractory malignancies [1]. By transforming a "stop" signal into a "go" signal, the CTBR12 receptor improves the persistence, survival, and cytotoxic potency of therapeutic cells in hostile tumor environments [2, 4].

Other names

CTBR12TGF-beta flip receptorTGF-beta switch receptorTGFBR2-IL12RB2 chimeraChimeric TGF-beta receptor

The receptor binds extracellular TGF-beta via the TGFBR2 domain and transduces an intracellular signal through the IL-12 receptor domain, activating the JAK-STAT pathway (specifically STAT4) to promote pro-inflammatory responses and immune cell effector function.