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Increasing the fitness of tumor-infiltrating T cells for cellular immunotherapy

Project description

T cells that are fit to fight cancer

Adoptive T cell therapies (ACTs) represent a promising anti-cancer strategy. The technology involves expansion of patient tumour-infiltrating lymphocytes (TILs) ex vivo, selection for the recognition of neoantigens, further expansion and infusion back into the patient. The fitness of T cells is crucial for the success rate of ACTs and for making the therapy accessible to cancer patients. The aim of the EU-funded TIL-FIT project is to increase the fitness of T cells by designing metabolic and pharmacological treatments based on proteomic profiles of TILs from liver cancer patients. Researchers will use machine-learning algorithms for the extraction of signatures to predict the fitness of TILs. The project will provide a better understanding of the T cell response to liver cancer and will improve the success rates of personalised ACTs for solid tumours.

Objective

Adoptive T cell therapies (ACTs) are emerging as a promising strategy to treat cancer. Tumor-infiltrating lymphocytes (TILs) are expanded ex vivo, selected for recognition of neoantigens, further expanded and then infused back into patients. This procedure requires extensive culturing and expansion of TILs during which many T cell clonotypes are lost. As tumor-reactive TILs are often exhausted and tend to be overgrown by functional, non-specific T cells in culture, the chance to identify potent tumor-reactive T cells dramatically decreases. Moreover, extensive expansion of T cells diminishes their anti-tumor activity and persistence in the body after adoptive transfers. Thus, improving the fitness of T cells is crucial to increase the success rate of ACTs and make this therapy accessible to a broad spectrum of cancer patients. Our first aim is to increase the fitness of T cells by designing metabolic and pharmacological interventions based on proteomic profiles of TILs from patients with liver cancer. Second, we will use machine-learning algorithms for the extraction of signatures to predict whether TILs grow well in culture, require and respond to metabolic interventions, or cannot be revitalized and do not grow at all. To deal with non-growing T cells, we aim at establishing a microfluidics-based workflow to graft the entire T cell receptor (TCR) repertoire from thousands of non-growing TILs onto fast growing Jurkat cells. After selecting Jurkat cells that recognize neoantigens, their TCRs will be expressed on naïve T cells obtained from the patient’s blood that are fit and suitable for ACT. This project will contribute to a better understanding of the T cell response to liver cancer and help increasing the success of personalized ACTs for solid tumors.

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2018-STG

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Host institution

FONDAZIONE PER L'ISTITUTO DI RICERCA IN BIOMEDICINA
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.

€ 1 406 250,00
Address
VIA FRANCESCO CHIESA 5
6500 BELLINZONA
Switzerland

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Region
Schweiz/Suisse/Svizzera Ticino Ticino
Activity type
Research Organisations
Links
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.

€ 1 406 250,00

Beneficiaries (1)

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