SubsidieMeestersNext generation, off-the-shelf, non fratricide-directed, CAR immunotherapy for relapse/refractory T-cell acute lymphoblastic leukemia
The project aims to develop a cost-effective immunotherapy for R/R T-ALL by dual targeting specific antigens using scalable, off-the-shelf CORD-GDT cells to improve patient outcomes.
Projectdetails
Introduction
R/R T-ALL remains a major clinical challenge. Despite improved survival rates thanks to intensive chemotherapy regimens, event-free (EFS) and overall (OS) survival remains <70%, and R/R T-ALL has a particularly poor outcome.
Current Treatment Limitations
There are currently no potential curative options for R/R T-ALL beyond hematopoietic stem cell transplantation (HSCT) and conventional chemotherapy, which is linked to large trade-offs in toxicities. Sadly, >90% of patients with R/R T-ALL/LL ultimately die.
Challenges in Immunotherapy
Strategies targeting T-cell malignancies using immunotherapies (including CARTs) remain challenging because of the shared expression of target antigens between normal and malignant T-cells. This ultimately leads to life-threatening immunodeficiency due to T-cell aplasia and fratricide of CARTs, which limits their therapeutic efficacy.
Proposed Solution
Here, we propose a unique and innovative approach to address this unmet clinical need based on the dual targeting of two specific antigens with expression restricted to T-cell lymphoblasts.
Objectives of the Consortium
Our consortium aims to provide a cost-effective immunotherapeutic alternative for most of the R/R T-ALL patients by:
- Dual targeting of two non-fratricide antigens.
- Utilizing our scalable, HLA-independent, allogenic, off-the-shelf, proprietary platform of CORD-GDT cells.
This approach aims to overcome the challenges of harvesting sufficient numbers of functional effector T cells from multi-treated patients with advanced disease while avoiding the toxicities derived from other shared antigens between healthy and malignant T cells.
Experimental Approach
Our strategy will be preclinically assayed using cutting-edge experimental models. We will mature and scale up the proprietary platform of universal CORD-GDT cells redirected against these two non-fratricide antigens.
Expected Outcomes
This is expected to provide superior effector features and contribute to ad-hoc point-of-care treatment with cost-effective, ready-to-use, and off-the-shelf effector cells.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.497.500 |
| Totale projectbegroting | € 2.497.500 |
Tijdlijn
| Startdatum | 1-4-2023 |
| Einddatum | 31-3-2026 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- ONECHAIN IMMUNOTHERAPEUTICS S.L.penvoerder
- INSTITUTO DE BIOLOGIA EXPERIMENTAL E TECNOLOGICA
- FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS
Land(en)
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