FINE-TUNING T CELL NETWORKS OF EXHAUSTION BY SYNTHETIC SENSORSbroad
T-FITNESS · Horizon Europe grant · 2022-09-01–2027-04-30
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call HORIZON-EIC-2021-PATHFINDERCHALLENGES-01 · scheme HORIZON-EIC · topic HORIZON-EIC-2021-PATHFINDERCHALLENGES-01-03. CORDIS record →
Objective
Cell and gene therapies offer a massive paradigm shift from current treatment options and hold the potential to cure previously untreatable diseases. Naturally-occurring and genetically modified T cells with chimeric antigen (CAR) or T cell receptors (TCR) have demonstrated remarkable curative capacities against advanced hematologic malignancies but have shown limited efficacy in treating solid tumors. Major barriers hindering the full antitumor potential of T cells are the immunosuppressive signals and persisting antigenic stimuli within the tumor microenvironment that inexorably push T cells into a highly dysfunctional state called “exhaustion”. Herein, we propose a groundbreaking technology, T-FITNESS, which will enable antitumor T cells to become refractory to exhaustion. At the core of the platform are microRNA (miRNA)-based synthetic logic circuits capable of rewiring the transcriptional networks orchestrating T cell exhaustion. By harnessing the power of CRISPR/Cas genome editing, we will integrate sensors of miRNAs upregulated in exhausted cells into untranslated regions of one or more transcription factors driving T cell exhaustion, to enable their fine-tuned downregulation. We will validate the reprogramming efficacy of T-FITNESS by performing extensive functional analyses in vitro and in vivo and advance the best circuits towards the clinic by developing an automated cGMP-compliant manufacturing process for point-of-care production of T-FITNESS-edited CAR-T cells. To develop this innovative platform, we will bring together a multidisciplinary consortium of academic and industry partners that combine their unique expertise in T cell therapy and immunology, synthetic biology, genome editing, cGMP manufacturing, bioinformatics, and communication. Easily integrable within CAR-T, TCR-T, and tumor-infiltrating lymphocyte (TIL) platforms, T-FITNESS will unleash the curative potential of T cell therapy for the benefit of an ever-growing number of cancer patients.
Beneficiaries (8)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| STIFTUNG LEIBNIZ-INSTITUT FUR IMMUNTHERAPIE | DE | coordinator | €946,651 | |
| MILTENYI BIOTEC BV & CO KG | DE | participant | €754,050 | |
| FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER | ES | participant | €715,660 | |
| FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA | IT | participant | €710,375 | |
| KEMIJSKI INSTITUT | SI | participant | €546,188 | |
| CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS | FR | participant | €480,163 | |
| INNOVATION ACTA SRL | IT | participant | €234,739 | Yes |
| EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH | CH | associatedPartner | — |
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