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Chimeric Antigen Receptor to generate Alloantigen-specific Regulatory T cells and promote allograft tolerance

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 CD4+FOXP3+ 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.

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-GF - Global Fellowships

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 171 349,20
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 171 349,20

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