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

CARxALL · Horizon Europe grant · 2023-04-01–2026-07-31

EC contribution

€2,497,500

Total cost

€2,497,500

Beneficiaries

3
About the data

Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call HORIZON-EIC-2022-TRANSITION-01 · scheme HORIZON-EIC · topic HORIZON-EIC-2022-TRANSITIONOPEN-01. CORDIS record →

Objective

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. 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. 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.

Beneficiaries (3)

OrganisationCountryRoleEC contributionSME
ONECHAIN IMMUNOTHERAPEUTICS S.L. ES coordinator €1,497,500 Yes
INSTITUTO DE BIOLOGIA EXPERIMENTAL E TECNOLOGICA PT participant €1,000,000 Yes
FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS ES thirdParty €0

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