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Drivers and Brakes of CAR T Cell Efficacy Determined by the Tumor Immune Microenvironment

Objective

Cancer immunotherapies with chimeric antigen receptor (CAR) T cells have shown dramatic clinical efficacy in patients with B cell neoplasms. Thus, their clinical use is expected to increase considerably in the near future. However, for poorly understood reasons, not all patients with lymphoma benefit from these expensive therapies. The ability to stratify patients into probable responders vs. non-responders prior to immunotherapy will improve treatment efficacy, limit patient exposure to adverse effects, and mitigate the significant economic costs associated with these therapies.
We and others have previously demonstrated that effective antitumoral immunity requires complex, spatially coordinated interactions between different cellular elements within the tumor immune microenvironment (TIME). There is evidence that patient response to immunotherapy is attributed to specific characteristics of the TIME, such as the composition, spatial arrangement, and activation states of immune cell types in it. Therefore, a better understanding of the TIME, and of how immunotherapies come into effect in live, intact human tissues, is critical for the selection of successful immunotherapies for our patients.
The overarching aim of the CAR-TIME project is to explore and visualize the cellular and molecular mechanisms of CAR T cell efficacy in lymphoma, determined by CAR T cell interactions with the TIME. This shall be achieved by creating a high-dimensional map of the TIME of diffuse large B cell lymphoma, performing live tissue cultures treated with immunotherapies, and establishing a novel live cell microscopy platform to interrogate intact human lymphoma tissue treated with CAR T cells. Drug perturbations, multidimensional imaging technologies, RNA sequencing and integrative bioinformatics analysis will illuminate mechanisms of therapy response vs. resistance, reveal novel predictive biomarkers, and inform future combination immunotherapy strategies to improve patient outcomes.

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

EBERHARD KARLS UNIVERSITAET TUEBINGEN
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.

€ 1 499 875,00
Address
GESCHWISTER-SCHOLL-PLATZ
72074 Tuebingen
Germany

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Region
Baden-Württemberg Tübingen Tübingen, Landkreis
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 499 875,00

Beneficiaries (1)

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