Temporal regulation of transgene expression controlled by amino acid availability in human T cells
2023
Aurore, Dougé | Cyrielle, Vituret | Valérie, Carraro | Laurent, Parry | Coudy-Gandilhon, Cécile | Pierre, Verrelle | Richard, Lemal | Combaret, Lydie | Julien, Averous | Céline, Jousse | Maurin, Anne-Catherine | Jacques-Olivier, Bay | Pierre, Fafournoux | Bruhat, Alain | Paul, Rouzaire | Unité de Nutrition Humaine (UNH) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
International audience
显示更多 [+] 显示较少 [-]英语. T cell therapy strategies, from allogenic stem cell transplantation toward genetically-modified T cells infusion, develop powerful anti-tumor effects but are often accompanied by side effects and their efficacy remain sometimes to be improved. It therefore appears important to provide a flexible and easily reversible gene expression regulation system to control T cells activity. We developed a gene expression regulation technology that exploits the physiological GCN2-ATF4 pathway ability to induce gene expression in T cells in response to one essential amino acid deficiency. We first demonstrated the functionality of NUTRIREG in human T cells by transient expression of reporter genes. We then validated that NUTRIREG can be used in human T cells to transiently express a therapeutic gene such as IL-10. Overall, our results represent a solid basis for the promising use of NUTRIREG to regulate transgene expression in human T cells in a reversible way, and more generally for numerous preventive or curative therapeutic possibilities in cellular immunotherapy strategies
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