Project description
Developing innovative and comprehensive cancer immunotherapies
Checkpoint blockade immunotherapy has revolutionised cancer treatment. However, this therapy only benefits a fraction of patients (< 15 %), and it does not selectively activate cancer-reactive T cells. The EU-funded RARITY project aims to find innovative solutions for the development of effective immunotherapies for patients who do not respond to current treatments. Researchers will detect and isolate cancer-reactive T cells from tumour tissues and develop them into highly effective therapies. Screening of non-exomic genomic regions will allow detection of unannotated proteins which result from de novo transcription and translation events and can be targeted by personalised immunotherapies. Finally, RARITY will dig into immune cell subsets other than T cells for potential complementary strategies to T cell immunotherapies.
Objective
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.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- social scienceseconomics and businessbusiness and managementemployment
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
2333 ZA Leiden
Netherlands