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Innovative CAR immune cell communities to break solid tumor barriers

Objective

Glioblastoma is the most common and most aggressive primary brain tumor in adults. It is paradigmatic for many incurable, poorly immunologic solid tumors that desperately need more effective therapies. Cellular immunotherapies with engineered immune cells expressing synthetic chimeric antigen receptors (CAR) to recognize cancer cells have great therapeutic potential. However, significant barriers related to cell manufacturing, immune cell migration and activation in the tumor environment and failure to engage the host immune system, have hindered the breakthrough of CAR cell therapies against solid tumors like glioblastoma. Our recent research shows encouraging results by combining different CAR immune cell types or arming them to co-express additional factors. Yet due to technical limitations, such multicellular CAR immune cell networks remain largely unexplored and the most potent factors for improving CAR immune cell efficacy in glioblastoma are still to be identified.
The overarching goal of this proposal is to break barriers of current CAR cell therapies in solid tumors with a focus on glioblastoma. To achieve this, we will employ innovative cell engineering strategies to create multicellular CAR immune cell networks and evaluate their safety and efficacy in advanced human model systems and orthotopic immunocompetent mouse models using cutting-edge technologies such as functional single-cell profiling (Aim 1). Furthermore, we will use in vivo cell labeling and time-resolved single-cell RNA sequencing to decipher the dynamics of a CAR cell therapy-associated host immune response and harness this for combination therapies (Aim 2) and conduct novel gain-of-function screens in primary immune cells to identify the most potent co-factor for enhancing CAR cell efficacy (Aim 3). Altogether our project will deliver novel cell therapy concepts and technical solutions to address unmet medical needs and provide novel insights in cancer-immune interactions.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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-2025-STG

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Host institution

UNIVERSITAT ZURICH
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.

€ 1 498 153,00
Address
RAMISTRASSE 71
8006 Zurich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
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.

€ 1 498 153,00

Beneficiaries (1)

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