Chimeric cytokine receptor provides IL-2 signaling for engineered regulatory T cell therapy

Abstract Regulatory T cells (Tregs) are potent immune suppressors and critical to the maintenance of immunological tolerance. Interleukin 2 (IL-2) is essential for Treg survival, expansion, phenotypic stability, suppressive function. However, Tregs do not produce IL-2 dependent on exogenous sources IL-2. This poses a significant challenge cell therapies in tissues with no or limited availability microenvironment. Therefore, we have developed engineered containing chimeric cytokine receptor that provides an signal. The receptor, termed IL-9 tethered switch (IL-9TSR), consists interleukin 9 (IL-9) extracellular domain IL9RA paired intracellular IL2RB. We shown expressing IL-9TSR can survive expand absence vitro vivo but require TCR stimulation prolonged persistency. stable FOXP3 +HELIOS +phenotype superior function when compared control Tregs. In conclusion, generated low environment. equipped signaling enable increased persistency allow potential use more clinical indications than previously possible.