Objective 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. Fields of science medical and health scienceshealth sciencesinflammatory diseasesnatural scienceschemical scienceselectrochemistryelectrolysismedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologyimmunotherapy Keywords interleukin-2 regulatory T cells oxidation specific epitopes inflammation cardiovascular diseases atherosclerosis myocardial infarction autoimmune diseases inflammatory diseases SLE Programme(s) HORIZON.2.1 - Health Main Programme HORIZON.2.1.4 - Infectious Diseases, including poverty-related and neglected diseases Topic(s) HORIZON-HLTH-2022-DISEASE-06-02-two-stage - Pre-clinical development of the next generation of immunotherapies for diseases or disorders with unmet medical needs Call for proposal HORIZON-HLTH-2022-DISEASE-06-two-stage See other projects for this call Funding Scheme HORIZON-RIA - HORIZON Research and Innovation Actions Coordinator SORBONNE UNIVERSITE Net EU contribution € 796 000,00 Address 21 rue de l'ecole de medecine 75006 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Participants (8) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Net EU contribution € 749 750,00 Address Rue de tolbiac 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 MEDIZINISCHE UNIVERSITAET WIEN Austria Net EU contribution € 731 220,00 Address Spitalgasse 23 1090 Wien See on map Region Ostösterreich Wien Wien Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES France Net EU contribution € 948 216,25 Address Rue leblanc 25 75015 Paris See on map Region Ile-de-France Ile-de-France Paris Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITA DEGLI STUDI DI TRIESTE Italy Net EU contribution € 399 765,00 Address Piazzale europa 1 34127 Trieste See on map Region Nord-Est Friuli-Venezia Giulia Trieste Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITATSKLINIKUM SCHLESWIG-HOLSTEIN Germany Net EU contribution € 334 000,00 Address Ratzeburger allee 160 23562 Lübeck See on map Region Schleswig-Holstein Schleswig-Holstein Lübeck, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. UNIVERSITAET zu LUEBECK Germany Net EU contribution € 6 250,00 Address Ratzeburger allee 160 23562 Lubeck See on map Region Schleswig-Holstein Schleswig-Holstein Lübeck, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 ILTOO PHARMA France Net EU contribution € 1 040 375,00 Address 14 rue des reculettes 75013 Paris See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Ile-de-France Ile-de-France Paris Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 ICOSAGEN CELL FACTORY OU Estonia Net EU contribution € 600 000,00 Address Eerika tee 1 61713 Kambja vald See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Eesti Eesti Lõuna-Eesti Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all KING'S COLLEGE LONDON United Kingdom Net EU contribution € 0,00 Address Strand WC2R 2LS London See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
