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Translating a Multi-Organ NAM into an Industrial Standard for Safety Assessment of Hematopoietic Stem Cell-Based Gene Therapies

Objective

Gene therapies (GTs) based on hematopoietic stem and progenitor cells (HSPCs) hold great promise, but their tumorigenicity risk, already observed in patients, is a significant concern. Current safety tests rely on oversimplified in vitro systems, often based on murine cells, and in vivo mouse models, which poorly reflect human biology and therefore lack sufficient predictivity. Starting from the output of the CRACK IT CleanCut Challenge of the NC3Rs, sponsored by leading industries that contributed to shaping the NAM development, STEM-SAFE aims to validate our disruptive MOAB-BM-LN, a dual-organ in vitro assay that recreates essential features of human bone marrow and lymph nodes. By detecting preleukemic events, our NAM enables evaluation of the actual GT products under physiologically relevant conditions. Uniting a world-class multidisciplinary team with access to unique real-world GT facilities, Fondazione Telethon (FTELE) within STEM-SAFE brings a bold vision to transform the preclinical testing service market of advanced therapy medicinal products. Our primary goal is to set a new analytical gold standard that addresses tumorigenic risks by reducing the need for animal testing with a more predictive and human-relevant in vitro assay. This assay has the potential to reduce development costs and accelerate the delivery of safer, life-saving therapies to patients while enhancing accessibility and setting an entirely new benchmark for success in the European GT industry. During phase 1, leveraging the collaboration with leading end users from the FTELE ecosystem and GT industry players committed to integrating the NAM into their GT development pipelines, we will demonstrate the viability of the NAM, advancing from TRL4 to TRL5 while elaborating the roadmap for adoption. In phase 2, following the regulatory plan and roadmap set in phase 1, we will transition the MOAB-BM-LN to a regulatory-qualified prototype suitable for broader adoption (TRL 6) and scale-up.

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HORIZON-EIC - HORIZON EIC Grants

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Call for proposal

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(opens in new window) HORIZON-EIC-2026-AIC

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Coordinator

FONDAZIONE TELETHON ETS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 300 000,00
Address
VIA VARESE 16/B
00185 ROMA
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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