Therapeutic Allele Engineering: A novel technology for cell therapy

Project Information

TALE

Grant agreement ID: 818806

DOI

10.3030/818806

Project closed

EC signature date 7 February 2019

Start date 1 June 2019

End date 31 May 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 397 082,00

EU contribution

€ 2 397 082,00

Coordinated by

UNIVERSITAT BASEL
Switzerland

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

Reporting period: 2023-12-01 to 2025-05-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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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