Project description
Multimodal treatment for malignant brain tumour in children
Paediatric high-grade glioma is the most common malignant brain tumour in children. Standard treatments often fall short, and new combination therapies are urgently needed, yet current options have done little to improve outcomes. The ERC-funded 4D-therapy project aims to create a targeted multimodal treatment for pHGG. It will combine drug therapies, radiotherapy, and innovative gene therapies to enhance treatment effectiveness and reduce side effects. The project will include initial screening and validation of a novel treatment regimen, detailed molecular profiling, and the use of adeno-associated viruses and CRISPR technology for precise targeting. Ultimately, it will establish effective treatment protocols for pHGG and provide insights into multimodal cancer therapy through preclinical studies with patient-derived models.
Objective
Paediatric high grade glioma (pHGG) is the most common malignant childhood brain tumour with standard-of-care inevitably resulting in therapy-resistant relapse or disease progression. The need for new combinatorial treatments is universally acknowledged; however, modern combination therapies are sparse, include at most two modalities and have so far not been able to significantly improve the dismal prognosis of the disease.
In this proposal, I conceptualize a highly targeted multimodal treatment strategy for pHGG (4D-therapy) based on complementary precision medicine approaches. The system leverages multiple inter-modal synergies, overcomes resistance to individual therapies and disperses off-targeting to different cell populations, thereby creating a large therapeutic window.
Initially, we will conduct a comprehensive screen to evaluate a novel regimen of combined upfront targeted drug- and radiotherapy (RT), followed by functional validation in vitro and in vivo. In-depth molecular profiling will allow us to unravel mechanisms of radiosensitization.
Further, we aim to establish an innovative gene therapy approach with unprecedented, highly specific tropism for tumour cells by combining elaborately selected adeno-associated viruses and nanocapsules with newly identified Cas-nucleases.
Ultimately, we will systematically combine drug-RTs, gene therapies and existing tumour-specific CAR-T cells within a rationally designed, multimodal treatment regimen and evaluate its efficacy in a series of preclinical studies. A broad representation of patient-derived xenografts, complemented by immunocompetent allograft models will provide leading-edge predictive power and a unique dataset to investigate multimodal interactions.
I expect this project to provide pioneering insights into inter-modal treatment synergies, to produce stratified treatment protocols for pHGG, directly informing clinical trials and to become a pathbreaking feasibility study for multimodal cancer therapy.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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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)
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Topic(s)
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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.
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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.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-STG
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69120 Heidelberg
Germany
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