Projektbeschreibung
Entwicklung innovativer und umfassender Krebsimmuntherapien
Zwar hat die Checkpoint-Blockade als Immuntherapie die Krebsbehandlung enorm vorangebracht, aber sie ist nur für einen Bruchteil der Patientinnen und Patienten (<15 %) geeignet, da keine selektive Aktivierung krebsreaktiver T-Zellen stattfindet. Das EU-finanzierte Projekt RARITY sucht nach innovativen Lösungen für wirksamere Immuntherapien für Patienten, die nicht auf heute übliche Therapien ansprechen. So wollen die Forschenden krebsreaktive T-Zellen in Tumorgewebe detektieren und isolieren, um daraus hochwirksame Therapien zu entwickeln. Durch Screening nicht-kodierender Genomabschnitte können nicht annotierte Proteine, die aus De-novo-Transkriptions- und Translationsereignissen hervorgehen, durch personalisierte Immuntherapien gezielt behandelt werden. Schließlich wird RARITY neben T-Zellen auch andere Untergruppen von Immunzellen untersuchen, um komplementäre Strategien zur T-Zell-Immuntherapie zu finden.
Ziel
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.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- social scienceseconomics and businessbusiness and managementemployment
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
2333 ZA Leiden
Niederlande