Descrizione del progetto
Sviluppo di immunoterapie antitumorali innovative e complete
L’immunoterapia con inibitori dei checkpoint ha rivoluzionato il trattamento del cancro. Tuttavia, questa terapia giova solo a una piccola parte dei pazienti (< 15 %) e non attiva selettivamente le cellule T reattive contro le cellule tumorali. Il progetto RARITY, finanziato dall’UE, si propone di trovare soluzioni innovative per lo sviluppo di immunoterapie efficaci per i pazienti che non rispondono ai trattamenti attuali. I ricercatori individueranno e isoleranno le cellule T reattive contro le cellule tumorali dai tessuti tumorali e le svilupperanno in terapie altamente efficaci. Lo screening delle regioni genomiche non codificanti permetterà di individuare le proteine non ancora annotate risultanti da eventi di trascrizione e traduzione de novo e che possono essere bersaglio di immunoterapie personalizzate. Infine, RARITY scaverà nei sottoinsiemi di cellule immunitarie diverse dalle cellule T per potenziali strategie complementari alle immunoterapie a cellule T.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- social scienceseconomics and businessbusiness and managementemployment
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
2333 ZA Leiden
Paesi Bassi