Temporal regulation of transgene expression controlled by amino acid availability in human T cells - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles (Data Paper) HLA: Immune Response Genetics Year : 2024

Temporal regulation of transgene expression controlled by amino acid availability in human T cells

Aurore Dougé
  • Function : Author
Cyrielle Vituret
Valérie Carraro
  • Function : Author
  • PersonId : 1305397
Laurent Parry
  • Function : Author
  • PersonId : 1155891
Cécile Coudy-Gandilhon
  • Function : Author
  • PersonId : 1137575
Richard Lemal
  • Function : Author
Anne‐catherine Maurin
  • Function : Author
Julien Averous
Jacques‐olivier Bay
  • Function : Author
Pierre Verrelle
  • Function : Author
Pierre Fafournoux
Alain Bruhat
Paul Rouzaire

Abstract

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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hal-04214017 , version 1 (09-11-2023)

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Aurore Dougé, Cyrielle Vituret, Valérie Carraro, Laurent Parry, Cécile Coudy-Gandilhon, et al.. Temporal regulation of transgene expression controlled by amino acid availability in human T cells. HLA: Immune Response Genetics, inPress, Jan: 103 (1), pp.e15252. ⟨10.1111/tan.15252⟩. ⟨hal-04214017⟩
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