Description du projet
Développer des immunothérapies innovantes et exhaustives contre le cancer
L’immunothérapie par inhibiteur de point de contrôle a révolutionné le traitement du cancer. Cependant, cette thérapie ne concerne qu’une fraction des patients (< 15 %), et elle n’active pas de manière sélective les cellules T réactives au cancer. Le projet RARITY, financé par l’UE, a pour objectif de trouver des solutions innovantes pour le développement d’immunothérapies efficaces pour les patients qui ne répondent pas aux traitements actuels. Les chercheurs vont détecter et isoler les cellules T réactives au cancer dans les tissus tumoraux et les transformer en thérapies très efficaces. Le dépistage des régions génomiques non exomiques permettra de détecter les protéines non annotées qui résultent d’événements de transcription et de traduction de novo et qui peuvent être ciblées par des immunothérapies personnalisées. Enfin, RARITY explorera des sous-ensembles de cellules immunitaires autres que les cellules T en vue d’éventuelles stratégies complémentaires aux immunothérapies à base de cellules T.
Objectif
Checkpoint blockade immunotherapies have revolutionized cancer treatment. However, this immunotherapy only benefits a minority of patients (< 15%), mainly those diagnosed with cancers having many mutations. Furthermore, checkpoint blockade therapy does not selectively activate cancer-reactive T cells.
RARITY responds to these shortcomings, aiming to provide innovative solutions for the development of effective immunotherapies for patients who do not benefit from current treatments. The ground-breaking preliminary data included in this application demonstrates that cancer-reactive T cells can be naturally present in so-called non-immunogenic cancers and that they acquire distinctive phenotypes. RARITY will apply state-of-the-art technologies to fingerprint these phenotypes. This will allow the isolation of cancer-reactive T cells from tumour tissues and their employment as highly-effective therapies. Therapeutic vaccination with cancer antigens can also be used to induce T cell responses in patients where natural activation of cancer-specific T cells is not detectable. However, the applicability of vaccination is compromised by the lack of specific targets, particularly in malignancies with few mutations. RARITY will address this problem by deploying a novel class of cancer antigens. An unprecedented screening of non-exomic genomic regions will be done to detect unannotated proteins that arise from de novo transcription and translation events. These proteins can then be targeted by personalized immunotherapies. Finally, thought-provoking findings included in RARITY suggest that immune cell subsets other than T cells play a major role in anti-tumour immune responses. These subsets need to be fully inventoried and categorised so that complementary strategies to T cell immunotherapies can be developed. RARITY will do so by conducting multidimensional analysis of cancer microenvironments using imaging mass cytometry and ex vivo modulation of immune responses.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- social scienceseconomics and businessbusiness and managementemployment
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
2333 ZA Leiden
Pays-Bas