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Developing novel single-cell technologies to model and perturb intra-tumor interactions and signaling – an innovation program for the next generation of immunotherapies

Project description

Engineering the immune system to attack tumour cells

Technology continues to be our greatest hope in the battle against cancer. The ERC-funded TROJAN-Cell project aims to develop single-cell genomic technologies to meticulously study the signalling mechanisms involved when tumours suppress the immune system. The knowledge gained will render an entirely new type of synthetic immunology technology — a toolset with the ability to exploit the immune system to detect a tumour's immune-inhibitory signals and actuate a targeted and effective immune response against the tumour. In effect, it uses the tumour's own defence system against itself. This ground-breaking approach is expected to revolutionise immunotherapy against cancer, as well as offer new approaches to immune engineering, molecule manipulation, and immunotherapy.

Objective

Single-cell genomic technologies have transformed many fields of research. We here seek to do just that in synthetic-immunology and immunotherapy. At present, our understanding of the complex crosstalk within the tumor microenvironment (TME) is still piecemeal, as is our ability to effectively engineer the immune system to attack tumor cells in spite of the robust immune-suppression signaling of the tumor. In line, current immunotherapies are effective only in a small subset of tumor types and patients, emphasizing the dire need to better understand immune-suppressive mechanisms within the TME and develop new immunotherapy strategies. What if we could develop technologies that reprogram the immune system to suit our therapeutic needs? In TROJAN-Cell, we will do so by first uncovering fundamental principles of the immune-tumor niche using advanced single-cell multiomics tools and modelling approaches. This will then serve to develop TROJAN-Cella novel synthetic immunology technology for engineering circuits capable of sensing inhibitory-immune signals and generating a proportional self-regulated immune-activation responsethus using the tumors own pro-cancer signaling to eradicate it. In Obj.1 we will dissect the principles of the inhibitory crosstalk and signaling in the TME of diverse human tumors using our single-cell technologies PIC-seq and INs-seq. In Obj.2 we will screen and develop mice tumor models that recapitulate the human TME, which we will use to define the function of factors/circuits of interest. In Obj.3 we will develop TROJAN-Cell, a novel toolset for transforming tumor inhibitory signals into potent, highly specific anti-tumor immunity. Our research will greatly expand our understanding of the immune-inhibitory crosstalk in the TME and give rise to novel immune engineering approaches and molecules, which may serve as the next generation of cancer immunotherapies.

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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-2021-ADG

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Host institution

WEIZMANN INSTITUTE OF SCIENCE
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.

€ 2 500 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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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.

€ 2 500 000,00

Beneficiaries (1)

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