Engineered interleukin-2 receptor subunit beta (IL-2Rβ (engineered))

The engineered interleukin-2 receptor subunit beta (IL-2Rβ) is a modified version of the CD122 protein expressed on SYNCAR-001 T cells, which are CD19-targeted chimeric antigen receptor (CAR) T-cells (Synthekine, 2024). This receptor is a key component of an "orthogonal" cytokine-receptor system designed to bind specifically to STK-009, a pegylated, engineered IL-2 ligand, while remaining insensitive to endogenous wild-type IL-2 (Sockolosky et al., Science, 2018). The primary biological function of this engineered receptor is to facilitate the selective expansion and activation of SYNCAR-001 T cells in vivo upon administration of STK-009, thereby enhancing the anti-tumor activity of the CAR-T therapy (NCT05612035). Signaling through the engineered IL-2Rβ activates the JAK/STAT pathway, particularly STAT5, which is essential for T-cell survival and proliferation (Silva et al., Nature, 2019). This approach is currently being evaluated for the treatment of B-cell malignancies, such as non-Hodgkin lymphoma and chronic lymphocytic leukemia, where CAR-T cell persistence is often a limiting factor for long-term efficacy (Synthekine, 2023). By decoupling the therapeutic T-cell stimulation from the systemic effects of natural IL-2, this target allows for precise control over the cellular therapy's potency and longevity.

Other names

Orthogonal interleukin-2 receptor subunit betaoIL-2RβCD122 (engineered)STK-009 receptor

Selective activation and expansion of engineered T cells via the JAK/STAT signaling pathway upon binding of the orthogonal ligand STK-009.