CARxALL | Next generation, off-the-shelf, non fratricide-directed, CAR immunotherapy for relapse/refractory T-cell acute lymphoblastic leukemia

Summary
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 90% of patients with R/R T-ALL/LL ultimately die. 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, ultimately leading to life-threatening immunodeficiency due to T-cell aplasia and fratricide of CARTs, which limits their therapeutic efficacy.
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. Our consortium aims to provide a cost-effective immunotherapeutic alternative for most of the R/R T-ALL patients by the dual targeting of two tnon-fratricide antigens using our scalable, HLA-independent, allogenic, off-the-shelf, proprietary platform of CORD-GDT cells, thus overcoming 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 . Our strategy will be preclinically assayed using cutting-edge experimental models, and we will mature and scale-up the proprietary platform of universal CORD-GDT cells redirected against these two non-fratricide antigens, 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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101113067
Start date: 01-04-2023
End date: 31-03-2026
Total budget - Public funding: 2 497 500,00 Euro - 2 497 500,00 Euro
Cordis data

Original description

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 90% of patients with R/R T-ALL/LL ultimately die. 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, ultimately leading to life-threatening immunodeficiency due to T-cell aplasia and fratricide of CARTs, which limits their therapeutic efficacy.
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. Our consortium aims to provide a cost-effective immunotherapeutic alternative for most of the R/R T-ALL patients by the dual targeting of two tnon-fratricide antigens using our scalable, HLA-independent, allogenic, off-the-shelf, proprietary platform of CORD-GDT cells, thus overcoming 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 . Our strategy will be preclinically assayed using cutting-edge experimental models, and we will mature and scale-up the proprietary platform of universal CORD-GDT cells redirected against these two non-fratricide antigens, 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.

Status

SIGNED

Call topic

HORIZON-EIC-2022-TRANSITIONOPEN-01

Update Date

31-07-2023
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Horizon Europe
HORIZON.3 Innovative Europe
HORIZON.3.1 The European Innovation Council (EIC)
HORIZON.3.1.0 Cross-cutting call topics
HORIZON-EIC-2022-TRANSITION-01
HORIZON-EIC-2022-TRANSITIONOPEN-01 EIC Transition Open 2022