Orthogonal interleukin-2 receptor (oIL-2R)

The orthogonal interleukin-2 receptor (oIL-2R) is a synthetic, engineered cytokine receptor designed to respond exclusively to a specific, mutated version of interleukin-2 (orthogonal IL-2) while remaining unresponsive to native, endogenous IL-2. This system is primarily utilized in adoptive cell therapies, such as CAR-T cells, to allow for the selective expansion and activation of the therapeutic cells in the patient's body without stimulating the broader endogenous immune system. By decoupling the cytokine signal from natural physiological pathways, clinicians can precisely control the persistence and potency of engineered T cells using an exogenous "engineered payload" (the orthogonal cytokine). This approach aims to overcome the systemic toxicities typically associated with high-dose native IL-2 therapy, such as vascular leak syndrome and off-target immune activation. In clinical development, the oIL-2R is expressed on the surface of CAR-T cells, and its cognate ligand (e.g., STK-009) is administered to drive therapeutic efficacy in both hematological and solid tumors.

Other names

Orthogonal IL-2 receptorEngineered IL-2 receptoroIL2ROrthogonal cytokine receptor

Agonism of the orthogonal IL-2 receptor by an engineered orthogonal IL-2 ligand to selectively expand and activate engineered cell therapies (e.g., CAR-T cells) in vivo.