Interleukin 6 signal transducer (gp130) (gp130)

Interleukin 6 signal transducer (gp130) is a critical transmembrane protein that functions as the universal signaling subunit for the IL-6 cytokine family, including IL-6, IL-11, and leukemia inhibitory factor [1][2]. It mediates essential cellular processes such as growth, survival, and immune regulation through the activation of the Janus kinase (JAK) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways [2][3]. In the context of advanced immunotherapy, the engineered cGP130 module is a synthetic, constitutively active variant of gp130 integrated into Chimeric Antigen Receptor (CAR) constructs to provide autonomous, ligand-independent STAT3 signaling [4][5]. This engineering strategy aims to enhance CAR-T cell persistence, metabolic fitness, and resistance to exhaustion within the immunosuppressive tumor microenvironment, particularly in solid tumors [5][6]. While pharmacological inhibitors of the native gp130 pathway, such as Olamkicept or Bazedoxifene, are used to treat inflammatory diseases, the engineered cGP130 module represents a novel approach to intrinsic cell-state programming in oncology [4][7].

Other names

IL6STCD130IL-6 receptor subunit betacGP130Constitutively active gp130Oncostatin M receptor subunit alpha

The engineered cGP130 module functions as an intracellular signaling domain that triggers the JAK/STAT3 pathway independently of extracellular cytokine binding, thereby promoting T-cell survival and preventing exhaustion in CAR-T cell therapies.