CENTRIC-BRAIN
Financiado
Characterizing and harnessing tumor-reactive T cells in the brain
Personalized tumor immunotherapy - vaccines and T cell therapies - requires the selection of few immunogenic epitopes recognized by tumor-reactive T cell receptors (TCRs) from thousands of potential tumor antigens in each tumor. T...
Personalized tumor immunotherapy - vaccines and T cell therapies - requires the selection of few immunogenic epitopes recognized by tumor-reactive T cell receptors (TCRs) from thousands of potential tumor antigens in each tumor. This selection is a huge challenge, particularly in brain tumors, where access to tumor tissue is limited and tumor-infiltrating T cells (TILs) are sparse. CENTRIC-BRAIN will reverse this epitope-centric approach by directly harnessing tumor-reactive orphan TCRs from TILs for personalized brain tumor immunotherapy. Using human brain tumor tissue we have developed and experimentally validated predicTCR, a novel approach using machine learning and explainable AI to derive a classifier that predicts tumor-reactivity of such orphan TCRs based on the expression of signature genes with > 90% accuracy across multiple tumour entities. CENTRIC-BRAIN will employ predicTCR to develop a personalized adoptive cell therapy using transgenic T cells with tumor-specific TCRs and improved function. CENTRIC-BRAIN hypothesizes that the signature genes underlying predicTCR determine the phenotypic and functional properties of tumor-reactive T cells and that predicted tumor-reactive orphan TCRs can be employed for adoptive therapy with personalized TCR-transgenic T cells.Aim 1 will refine predicTCR by characterizing the transcriptional programs and spatial distribution of tumor-reactive T cells in human brain tumor samples. Aim 2 will define the functional relevance of transcriptional programs for tumor-reactive T cells in syngeneic humanized and patient-derived xenograft brain tumor models. Aim 3 will validate the predicted tumor-reactive orphan TCRs by adoptive transfer of T cells genetically engineered to express predicted tumor-reactive TCRs. CENTRIC-BRAIN will thus revolutionize precise and efficient implementation of personalized adoptive cell therapy for brain tumors using T cells expressing tumor-reactive patient-derived orphan TCRs.
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Duración del proyecto: 59 meses
Fecha Inicio: 2024-10-01
Fecha Fin: 2029-09-30
Fecha Fin: 2029-09-30
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-10-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 1 año
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5