Fig. 4
From: New insights into the stemness of adoptively transferred T cells by γc family cytokines
The engineered IL-2/IL-2R or IL-15/IL-15R for adoptively TSCM induction. A Engineered IL-2 for selectivity to dimeric intermediate-affinity IL-2R and TSCM induction. Activated T cells with high-affinity IL-2R finally go towards apoptosis by IL-2, and Treg with constitutively IL-2Rα deprive T cells of IL-2 to impair cytotoxicity. Reducing the affinity of IL-2 for IL-2Rα or increasing affinity for IL-2Rβ could target dimeric intermediate-affinity IL-2R and generate an appropriate affinity for TSCM induction by further lowering the signal level. Applying to CAR-T engineering, engineered orthogonal IL-2 and IL-2Rβ system or fused protein will be expressed to function CAR-T cells to induce TSCM. B Engineered mIL-15 armored CAR-T cell for stemness maintenance. The trans-presentation of IL-15 by IL-15Ra on APC to T cells contributes to TSCM induction independent of antigen stimulation. As a result, co-expressing IL-15 and IL-15Ra phenocopy the special presentation by a linker, yielding membrane-bounding IL-15. The mIL-15- CAR-T cells are able to differentiate into TSCM in vivo