Therapeutic Allele Engineering: A novel technology for cell therapy

Información del proyecto

TALE

Identificador del acuerdo de subvención: 818806

DOI

10.3030/818806

Proyecto cerrado

Fecha de la firma de la CE 7 Febrero 2019

Fecha de inicio 1 Junio 2019

Fecha de finalización 31 Mayo 2025

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 2 397 082,00

Aportación de la UE

€ 2 397 082,00

Coordinado por

UNIVERSITAT BASEL
Switzerland

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

Período documentado: 2023-12-01 hasta 2025-05-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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