Objective
Despite major advances in cancer immunotherapy, most patients still lack durable benefit. Tumor-infiltrating T lymphocyte (TIL) therapy can induce deep cancer remissions, but potency varies and complete clinical responses are limited to 20%. Crucially, although truly tumor-reactive T cells are rare in cancers (<5%), current manufacturing protocols expand TILs in bulk, without inclusion of a selection or enrichment step. Together, these observations create both a dire clinical need and unique opportunity to augment the impact of this type of immunotherapy, namely by selecting the actively tumor-killing T cells.
In our current ERC Advanced project ReverT, we discovered that tumor-killing T cells are strongly enriched in so-called heterotypic cell clusters: tight conjugates of T cells with tumor (melanoma) cells and/or antigen-presenting cells. We developed an isolation procedure to capture intact clusters straight from clinical cancer specimens from patients. These T cell clusters can be effectively expanded and exhibit a 9-fold increase in tumor-killing activity against patient tumors.
This ERC PoC project translates our findings into a “CLUSTER-TIL” manufacturing module, integrating upstream of the standard production pipeline to enable enhanced TIL therapy. We will develop and optimize a scalable procedure to purify cluster-derived T cells from tumor digests from patients, define quality metrics for tumor reactivity and benchmark to the standard bulk TIL workflow. CLUSTER-TIL will deliver a highly potent, consistent anti-cancer T cell therapy that will be tested in a planned investigator-initiated Phase 2a trial in melanoma. We observe similar clusters in other solid tumor types, enabling expansion to patient groups beyond melanoma. Furthermore, two patent applications protect the CLUSTER-TIL technology. This PoC will also generate follow-on IP to support a spin-off applying the technology for broader clinical implementation and improved patient outcomes.
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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-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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2026-POC
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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.
1066 CX Amsterdam
Netherlands
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.