Objectif Immunotherapy is expected to fundamentally change the treatment of cancer patients. Personalized vaccines elicitingimmune responses against individual cancer mutations have moved into the spotlight. We have pioneered the field andmoved ´cancer mutanome vaccines´ from a mere vision into a disruptive medical concept compatible with currentstandards of drug development and health care practice. Solving key scientific and technological challenges and buildingon extensive preclinical studies, we showed in a first-in-human trial potent tumor-directed immunity in every singlevaccinated patient, and clinical activity of a novel mRNA-based mutanome vaccine. Given that mutations are a hallmarkof cancer, mRNA mutanome vaccines are universal drugs the efficacy of which are unaffected by the cancer type. Theaim of this proposal is to ignite the next wave of advancement by addressing four key constraints challenging a full clinicalrealization of such vaccines. We will address the scarcity of point mutations in many tumors by extending neoepitopediscovery to the full spectrum of genetic aberrations. Cancers are heterogeneous and outgrowth of clones unaccountedfor by the vaccine is an efficient escape mechanism. We will develop neoepitope prediction algorithms deciphering clonalheterogeneity to inform rational vaccine design and countermeasures against selection of target escape variants. Tumorcell resistance to vaccine-induced T cells due to antigen presentation defects will be addressed by developing strategiesfor mobilizing the full repertoire of immune effector mechanisms, including antibodies and NK cells. T-cell exhaustion willbe tackled by vaccination protocols promoting long-lived memory responses and by combination treatments counteractingtumor-mediated immunosuppression. Finally, we will drive the seamless clinical translation of the scientific findings byclose interdisciplinary collaboration with strong and established clinical and industrial partners. Champ scientifique medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Mots‑clés Precision Medicine Personalized Cancer Vaccines Neoepitope Prediction Cancer Mutanome Immune Escape Tumor Heterogeneity Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2017-ADG - ERC Advanced Grant Appel à propositions ERC-2017-ADG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil TRON - TRANSLATIONALE ONKOLOGIE ANDER UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ GEMEINNUTZIGE GMBH Contribution nette de l'UE € 2 482 500,00 Adresse FREILIGRATHSTRASSE 12 55131 Mainz Allemagne Voir sur la carte Région Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 482 500,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire TRON - TRANSLATIONALE ONKOLOGIE ANDER UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ GEMEINNUTZIGE GMBH Allemagne Contribution nette de l'UE € 2 482 500,00 Adresse FREILIGRATHSTRASSE 12 55131 Mainz Voir sur la carte Région Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 482 500,00
