Chimeric Transforming Growth Factor-beta Signal Receptor (CTSR)

The Chimeric Transforming Growth Factor-beta Signal Receptor (CTSR) is an engineered synthetic receptor designed to enhance the efficacy of adoptive cell therapies, such as TCR-T and CAR-T cells, particularly within the hostile environment of solid tumors. In many cancers, the cytokine TGF-beta is secreted at high levels to suppress the immune system by inhibiting T-cell proliferation and function through the SMAD signaling pathway. The CTSR functions as a 'switch receptor' by fusing the extracellular TGF-beta binding domain to an intracellular stimulatory domain, such as that of the IL-7 receptor. This architecture allows the engineered T-cell to capture the inhibitory TGF-beta signal and convert it into a potent growth and survival signal, effectively turning a tumor's defense mechanism into a therapeutic advantage (Medigene AG, 2024). By neutralizing local immunosuppression and simultaneously providing co-stimulation, CTSR-equipped cells demonstrate improved persistence and anti-tumor activity in preclinical models of solid malignancies. Clinical candidates utilizing this technology, such as MDG1015, are currently being evaluated for their ability to overcome the barriers presented by the tumor microenvironment (ClinicalTrials.gov, 2023).

Other names

Chimeric TGF-beta receptorTGF-beta switch receptorTGFBR2-IL7R fusion receptorChimeric TGFβ Signal Receptor

The CTSR is a synthetic fusion protein that combines the extracellular binding domain of the TGF-beta receptor (typically TGFBR2) with the intracellular signaling domain of an immunostimulatory receptor, such as the IL-7 receptor alpha (IL-7Rα). When TGF-beta binds to the extracellular domain, instead of triggering the canonical inhibitory SMAD signaling pathway, the receptor initiates stimulatory signals (e.g., STAT5 activation) that promote T-cell activation and persistence (Medigene AG, 2023; Schober et al., 2020).