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Epigenetic fine-tuning of T cells for improved adoptive cell therapy

Project information

Grant agreement ID: 803992

Status

Ongoing project

  • Start date

    1 January 2019

  • End date

    31 December 2023

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 489 725

  • EU contribution

    € 1 489 725

Hosted by:

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany

Objective

"Adoptive T cell therapy is a promising approach in various clinical settings, from target-specific immune reconstitution fighting cancer and chronic infections to combating undesired immune reactivity during auto-immunity and after organ transplantation.
However, its clinical application is currently hampered by: 1) the acquisition of senescence during the required in vitro expansion phase of T cells which limits their survival and fitness after infusion into the patient, and 2) the functional plasticity of T cells, which is sensitive to the inflammatory environment they encounter after transfusion and which might result in a functional switch from the desired effect (e.g. immunosuppressive) to the opposite one (pro-inflammatory).
I want to tackle these obstacles from a new molecular angle, utilizing the profound impact of epigenetic mechanisms on the senescence process as well as on the functional imprinting of T lymphocytes. Epigenetic players such as DNA methylation essentially contribute to T cell differentiation and harbor the unique prospect to imprint a stable developmental and functional state in the genomic structure of a cell, as we could recently show in our basic immune-epigenetic studies. Therefore, I here propose to equip T lymphocytes with the required properties for their successful and safe therapeutic application, including their functional fine-tuning according to the clinical need by directed modifications of the epigenome
('Epi-tuning').
To reach these goals I want: 1) to reveal strategies for the directed manipulation of the epigenetically-driven mechanism of cellular senescence and 2) to apply state-of-the-art CRISPR/Cas9-mediated epigenetic editing approaches for the imprinting of a desired functional state of therapeutic T cell products. These innovative epigenetic ""one-shot"" manipulations during the in vitro expansion phase should advance T cell therapy towards improved efficiency, stability as well as safety."

Host institution

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Address

Chariteplatz 1
10117 Berlin

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 489 725

Beneficiaries (1)

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany

EU Contribution

€ 1 489 725

Project information

Grant agreement ID: 803992

Status

Ongoing project

  • Start date

    1 January 2019

  • End date

    31 December 2023

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 489 725

  • EU contribution

    € 1 489 725

Hosted by:

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany