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Targeting innate immunity to induce TOLERANCE in transplantation

Project description

Immunological tolerance: the holy grail of transplantation

Organ transplantation undoubtedly offers a life-saving option for patients suffering from end-stage organ failure. However, chronic rejection of allogeneic grafts and side effects associated with long-term use of immunosuppressive drugs pose serious restrictions to transplant patients’ quality of life. While classically the therapeutic focus is on adaptive immunity, the working hypothesis of the EU-funded TOLERANCE project is that the answer to successful allogeneic transplantation lies in innate immunity. Researchers will study a kidney transplant patient biobank to develop new methods for targeting innate immunity. Project results will pave the way towards immunotherapies and novel immunoimaging strategies for promoting graft tolerance in transplantation.

Objective

Transplantation is a life-saving procedure for patients who suffer from end-stage organ failure. While the discovery of potent immunosuppression offers a solution to the previously insurmountable problem of organ rejection, transplant recipients still face substantial problems, including chronic rejection and adverse effects related to the chronic use of immunosuppressive drugs. Therefore, transplantation field’s ‘holy therapeutic grail’ is immunological tolerance induction without the need
for chronic immunosuppression.
Our recent work has identified innate immune responses, and in particular trained immunity, to play a critical role in transplantation. Based on compelling preliminary data, I hypothesize that trained immunity-induced myelopoiesis and hyperinflammation are proximal causes of T and B cell immunity and therefore are compelling therapeutic targets to induce immunological tolerance and significantly
improve allograft survival.
We will tackle the central hypothesis from the vantage points of medicine & immunology and biomedical engineering by pursuing two objectives: Objective 1 Medicine & Immunology – To mechanistically decipher innate immune responses and myelopoiesis in kidney transplant patients. Objective 2 Biomedical Engineering – To develop immuno-imaging and nanomedicine approaches that target innate immunity in transplantation. We have developed a comprehensive preclinical development program to evaluate these novel methods in a kidney transplant mouse model.
This Program’s successful completion will yield unique nanobiologic immunotherapies and immunoimaging strategies, which can be employed to take control of the innate immune response and promote allograft tolerance in transplantation, but can also be adopted to treat other conditions that are characterized by an exacerbated immune response, including infections, cancer and
cardiovascular diseases.

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Topic(s)

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2020-ADG

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Host institution

TECHNISCHE UNIVERSITEIT EINDHOVEN
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.

€ 1 020 910,00
Address
GROENE LOPER 3
5612 AE Eindhoven
Netherlands

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Region
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 020 910,00

Beneficiaries (2)

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