Therapeutic Allele Engineering: A novel technology for cell therapy

Informations projet

TALE

N° de convention de subvention: 818806

DOI

10.3030/818806

Projet clôturé

Date de signature de la CE 7 Février 2019

Date de début 1 Juin 2019

Date de fin 31 Mai 2025

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 397 082,00

Contribution de l’UE

€ 2 397 082,00

Coordonné par

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 4 - TALE (Therapeutic Allele Engineering: A novel technology for cell therapy)

Période du rapport: 2023-12-01 au 2025-05-31

Résumé du contexte et des objectifs généraux du projet

Recent advances in genetics, cell biology and immunology research have translated into highly efficient cell-based therapeutics. The reprogramming of immune killer cells to recognise B cell leukaemias has brought unprecedented clinical responses in treatment-resistant cases. However, a fundamental problem of today’s cell therapies is that transferred and host cells cannot be distinguished in the course of the treatment. Solving this problem could enable new therapeutic approaches and thus benefit society.

The EU-funded TALE project aimed to introduce novel "allele engineering" technology to improve the safety and efficacy of human cell therapies. The objective was to engineer minor changes into proteins expressed by therapeutic cells without changing the protein's or the cell's function. The engineered cells were supposed to become invisible to a targeted therapy. The targeted therapy would then selectively kill the diseased cells (e.g. leukemia cells) but leave the therapeutic cells untouched. The project aimed to demonstrate the feasibility and usefulness of this new approach to treat a model of acute myeloid leukemia (AML) and go beyond cancer therapies.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Over the course of the project we rationally designed allele engineering solutions for multiple target proteins. We continuously improved our approaches and validated the protective effect of the engineered protein variants. Using cutting-edge molecular genome engineering tools, we successfully engineered the designed variants into relevant primary cell types such as T cells and blood stem cells. We demonstrated in multiple AML models in vivo in mice that the approach enabled tumor cell eradication without affecting the engineered, therapeutic cells.

We presented the work at many scientific conferences, published high profile scientific manuscripts, filed several patents, founded a spin-off company and licensed the technology to biotech companies.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The results obtained are in line with the initially proposed objectives. We confirmed the feasibility and utility of this newly developped approach. The selectivity of this tumor treatment went beyond the state of the art and is close to clinical translation. Furthermore, our results opened new avenues to further develop allele engineering for additional applications beyond cancer, e.g. genetic blood diseases.

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