Nanostring gene expression profiling of TurboCAR T cells

IL2 and IL15 both utilize IL2Rβ and the common gamma chain (γc) and trigger near-indistinguishable downstream signaling pathways. Yet, IL2 and IL15 differentially regulate T cell metabolism and consequently dictate distinct functional outcomes, with IL2 promoting glycolysis and exhaustion, and IL15 favoring oxidative phosphorylation and long-term persistence. Since TurboCAR.15 variants contain signaling domains derived from IL2Rβ, we sought to determine whether they more closely recapitulated IL2 or IL15 signaling. To this end, gene expression profiles of TurboCAR.15 variants versus BCMA TurboCARs that had been conditioned and cultured in IL2 or IL15 were compared. Unmodified CAR T cells that had been conditioned and cultured with no cytokines, IL2, or IL15, as well as two TurboCAR.15 variants from 2 donors were analyzed.