Objective
Adoptive T cell therapies are a new class of living drugs, achieving durable results in a subset of patients with aggressive malignancies. These transformative outcomes are not shared with the majority of patients with solid tumors that remain resistant to current T cell therapies. As engineered T cell therapy is usually directed against a single antigen, it is especially vulnerable to antigen loss as a tumor resistance mechanism. Moreover, cancer immunotherapy often leads to severe immune-related adverse events (irAE) by destructive self-reactivity that must be evaluated together with the therapeutic benefit. While T cell therapies with tumor-infiltrating lymphocytes might circumvent these shortcomings, tumor tissue availability is limited and T cells are poorly responsive to ex-vivo perturbation. These therapeutic challenges highlight the gaps in our knowledge of how to engineer curative anti-tumor immunity.
We recently developed foundational platforms for CRISPR engineering, TCR repertoire manipulation, and single-cell omics of primary human T cells. We plan to leverage these opportune achievements to address the critical gaps in adoptive T cell therapies. We will focus on three important aspects of engineered anti-tumor immunity: efficacy, safety, and specificity. We will tune TCR sensitivity by perturbing key genes to determine how TCR signaling balances burst-like effector function and long-term persistence. We will also reveal the sequestered self-reactive T cell compartment to control for irAE following immunotherapy. Finally, we will directly uncouple anti-tumor TCR repertoires from their dysfunctional state to mount a polyclonal anti-tumor immune response. This strategy is radically different from current T cell therapies as it is agnostic to specific tumor antigens and leverages pre-existing polyclonal antitumor immunity. These studies will chart novel blueprints for robust, safe, and specific engineered cell therapies targeting solid tumors.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-STG
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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.
69978 Tel Aviv
Israel
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.