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Personalized molecular reprogramming of the tumor immune microenvironment and engineered adoptive cell transfer in synergy with ion-beam radiotherapy for next-generation curative cancer treatments

Objective

Cancer is a complex multifaceted disease. To conquer cancer, a multidisciplinary approach for rational design of multimodal therapies is imperative. Ground-breaking discoveries in immunotherapy and precision radiotherapy (RT) coupled with initial encouraging results of their combined application, have engendered hope that curative cancer treatments may become possible. Our objective is to harness the full synergistic potential of both modalities through deeper comprehension of the tumor immune microenvironment (TIME) evolution in response to therapy selection pressures. We propose innovative strategies to overcome five major obstacles limiting immunotherapy success: i) tumor camouflage from immune cell recognition, ii) limited immune cell homing and tumor trafficking, iii) paucity of immune activating signals, iv) suppressive signals in the TIME, and v) failure to induce deep memory responses for durable antitumor immunity. The convergence of four research fields, each represented by pioneering scientists, provides a unique opportunity to revolutionize current cancer treatment. To reprogram TIME and create an immunopermissive tumor niche we will employ a broad spectrum of clinical-grade ion beams including protons, helium-, carbon-, and oxygen ions with unique biophysical properties. These novel beam qualities, combined with targeted molecular countermeasures against key tumor immune evasive mechanisms, such as interference with TGFbeta- and integrated stress response pathways, will establish an effective in situ cancer vaccination strategy. In synergy with RT-mediated TIME reprogramming, two adoptive immune cell therapies will be explored: personalized vaccine-induced T cells targeting tumor-specific intracellular neoantigens and chimeric antigen receptor (CAR) T cells engineered to specifically recognize tumor membrane-associated antigens. Our team is uniquely positioned worldwide to develop the next generation of precision immunoradiotherapy.

Fields of science (EuroSciVoc)

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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)

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-SYG - HORIZON ERC Synergy 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-SyG

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Host institution

UNIVERSITATSKLINIKUM 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.

€ 4 325 147,75
Address
IM NEUENHEIMER FELD 672
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
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.

€ 4 325 147,75

Beneficiaries (4)