Descripción del proyecto
Desarrollo de inmunoterapias integrales e innovadoras contra el cáncer
La inmunoterapia de bloqueo de puntos de control ha revolucionado el tratamiento del cáncer. Sin embargo, tan solo una pequeña parte de los pacientes (menos del 15 %) se beneficia de esta terapia, la cual no activa de forma selectiva los linfocitos T oncorreactivos. El proyecto financiado con fondos europeos RARITY busca encontrar soluciones innovadoras para el desarrollo de inmunoterapias eficaces para pacientes que no respondan a los tratamientos actuales. Los investigadores detectarán y aislarán linfocitos T oncorreactivos a partir de los tejidos tumorales y los desarrollarán para convertirlos en terapias muy eficaces. El cribado de regiones genómicas no exómicas permitirá detectar proteínas no anotadas que resulten de acontecimientos de traslación y transcripción «de novo» y a las que puedan dirigirse las inmunoterapias personalizadas. Por último, RARITY seguirá investigando sobre subconjuntos de células inmunitarias distintas a los linfocitos T para posibles estrategias complementarias a las inmunoterapias con linfocitos T.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- social scienceseconomics and businessbusiness and managementemployment
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
2333 ZA Leiden
Países Bajos