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Reversing Tumor Immunotherapy Resistance via TME Modulation

Objective

T cell infiltration and persistence in solid tumors are crucial for the success of T cell-based immunotherapies, yet the tumor microenvironment (TME) often suppresses T cell access and function. Our ERC-funded research has identified a G protein-coupled receptor (GPCR), activated by a metabolite commonly enriched in solid tumors, that substantially impairs T cells. We showed that inhibition of this GPCR enhances T cell infiltration, persistence, and cytotoxicity, thereby substantially improving the efficacy of CAR-T, TCR-T, and immune checkpoint blockade (ICB) therapies across tumor models of various cancer types.

To advance these findings towards clinical applications, we developed monoclonal antibodies (mAb) against this GPCR, which exhibit potent blocking functions and high specificity. Our lead mAb effectively reactivates patient-derived tumor-infiltrating lymphocytes (TILs) against autologous primary tumor cells, underscoring its therapeutic potential.

Project REVIVE aims to 1) humanize and optimize our mAbs target this GPCR, 2) conduct preclinical validation to assess efficacy and safety in advanced models, 3) develop predictive biomarkers for patient selection, and 4) establish a comprehensive intellectual property (IP) and commercialization strategy, integrating freedom to operate (FTO) analyses, market assessment, licensing opportunities, and industry partnerships to facilitate clinical translation.

By executing these steps, REVIVE will generate an investor-ready, clinically viable, IP-protected antibody targeting this GPCR, supported by comprehensive preclinical validation and a biomarker-driven patient selection strategy. These outcomes will enhance the commercial attractiveness of our therapeutic candidate for licensing or spin-out opportunities, paving the way for future clinical translation and patient benefit.

Fields of science (EuroSciVoc)

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

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.

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.

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2025-POC

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Host institution

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
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.

€ 150 000,00
Address
IM NEUENHEIMER FELD 280
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
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.

No data

Beneficiaries (1)

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