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PolyAntiTumor

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Polyclonal anti-tumor immunity by engineered human T cells

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 tumor... ver más

30/09/2027

TAU

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

TEL AVIV UNIVERSITY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-10-01

ERC-2021-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 3 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

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TAU

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Duración del proyecto: 59 meses Fecha Inicio: 2022-10-01
Fecha Fin: 2027-09-30

Líder del proyecto

TEL AVIV UNIVERSITY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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