CAR ART SIGNED

Project "CAR ART" data sheet

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 Project objective

Organ transplantation is the best life-supporting treatment for terminal organ failure. Graft survival is however limited by rejection, a destructive process resulting from the response of recipient’s immune system against donor specific alloantigens. Prevention of rejection currently relies on immunosuppressive drugs that lack antigen specificity and therefore increase the risk for infections and cancers. Induction of donor-specific tolerance would provide indefinite graft survival without morbidity and therefore represents the Grail of transplant immunologists. Tolerance has been obtained in experimental models with adoptive transfer of ex vivo-expanded CD4FOXP3 regulatory T cells (Treg). Preclinical studies have indicated that the potency and specificity of Treg therapy could be markedly enhanced by the use of Treg specific for donor alloantigens. Translation of this approach in the clinic has been hindered by the lack of clinically applicable strategies to generate sufficient numbers of potent donor-specific Tregs. To overcome this limitation, Pr Levings’ group (Child and Family Research Institute, Vancouver, Canada) has just recently successfully used chimeric antigen receptor (CAR) technology to redirect the specificity of human Treg toward a transplant-relevant antigen. The objective of the 2-year action is to assess the impact of alloantigen-specific CAR Treg on cellular and humoral alloimmune responses and their ability to promote allograft tolerance. The outgoing phase of the global fellowship will be performed in Pr Levings’ lab, and the return phase in Pr Glaichenhaus’ team (Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France) where the researcher will get in few years a tenured position. The main ambition of the program is to provide key data for the development of a clinical trial with CAR Tregs in kidney transplantation.