orthogonal IL-2

Orthogonal IL-2 (oIL-2) is an engineered, mutant variant of interleukin-2 (IL-2) designed to selectively bind and signal through a complementary, genetically engineered orthogonal IL-2 receptor (oIL-2Rβ) while exhibiting negligible interaction with wild-type IL-2 receptors. This 'lock-and-key' approach enables the selective activation, survival, and expansion of engineered adoptive cell therapies—such as CAR-T cells or regulatory T cells (Tregs)—in vivo without triggering the off-target immune activation and severe systemic toxicities (e.g., capillary leak syndrome) associated with wild-type IL-2. Originally developed at Stanford University, the technology has been licensed to Synthekine, which is clinically evaluating its human orthogonal IL-2 candidate, STK-009, in combination with SYNCAR-001 CAR-T cells.

Other names

hoIL-2hoIL2hoIL 2human orthogonal IL-2oIL-2oIL2oIL 2ortho-IL-2ortho-IL2ortho-IL 2orthoIL-2orthoIL2orthoIL 2orthogonal human IL-2orthogonal mutant IL-2