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Multimodal “4D”-therapy of pediatric high grade glioma

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.

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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

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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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.

€ 1 493 711,00
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.

€ 1 493 711,00

Beneficiaries (1)

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