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Financement de l’UE (5 605 576 €) : Développement préclinique d’une interleukine-2 de 3e génération ciblant les sites inflammatoires Hor01/06/2023 Programme de recherche et d'innovation de l'UE « Horizon »
Vue d’ensemble
Texte
Développement préclinique d’une interleukine-2 de 3e génération ciblant les sites inflammatoires
As major players in the regulation of immune responses, regulatory T cells (Tregs) are important therapeutic targets for autoimmune and inflammatory diseases. Interleukin-2 (IL-2) used at low doses (IL-2LD) stimulate and expand Tregs in vivo. While 1st-generation native IL-2LD are currently under extensive clinical evaluation, pharmaceutical companies are developing 2nd-generation IL-2 muteins with improved half-life and activity. We aim to develop 3rd-generation IL-2 specifically targeting inflammatory sites (IL-2IT) by using antibodies (Abs) against oxidation specific epitopes (OSE) that are both universal markers and mediators of inflammation. IL-2-OSE-Ab fusion proteins should allow dampening of local inflammation by a double-hit mechanism involving Ab neutralization of pro-inflammatory OSE and IL-2 stimulation of Tregs. As a proof of concept, we designed a first IL-2IT in which an IL-2N88R mutein is fused to an scFv from a prototypic anti-OSE Ab. This IL-2IT (i) binds to IL-2 receptors and OSE, (ii) has an extended half-life and (iii) superior therapeutic efficacy compared to native IL-2 in mice. Our general objectives are to design an optimized IL-2IT by testing combinations of different anti-OSE Ab with IL-2 and IL-2 muteins, and to complete its preclinical development in mice and macaques. We will validate the use of IL-2IT in cardiovascular diseases (CVD), i.e. atherosclerosis, vasculitis, myocardial infarction and SLE-associated CVD, as these conditions have been shown to be improved by Treg infusions, native IL-2 and OSE-Abs in mice. Carried by leading experts in the use IL-2, OSE-Abs, models of CVD, and clinical trials with native IL-2, the successful validation of an IL-2IT will open a new era for highly selective and effective immunotherapies based on Treg stimulation for diseases that represent a leading cause of death and morbidity. Furthermore, it will validate the broader concept of targeting any therapeutic molecule to inflammatory sites.
| King's College London | ? |
| Commissariat a L Energie Atomique et aux Energies Alternatives | 948 216 € |
| ICOSAGEN CELL FACTORY OÜ | 600 000 € |
| Iltoo Pharma | 1 040 375 € |
| Institut National de la Sante et de la Recherche Medicale | 749 750 € |
| Medizinische Universitaet Wien | 731 220 € |
| Sorbonne Universite | 796 000 € |
| Universita Degli Studi Di Trieste | 399 765 € |
| UNIVERSITAET zu LUEBECK | 0,00 € |
| UNIVERSITATSKLINIKUM SCHLESWIG-HOLSTEIN | 340 250 € |
https://cordis.europa.eu/project/id/101080897
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : King's College London UNIVERSITY, Londres, Royaume Uni.
