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Leveraging Polymer Therapeutics as Nanomedicine for Local Glioblastoma Immunotherapy

Project description

Improved glioblastoma nanomedicine

Glioblastoma multiforme (GBM) is an aggressive and highly invasive brain tumour characterised by poor prognosis and limited treatment options. The blood brain barrier poses a major limitation to the systemic administration of drugs while the suppressive immune microenvironment of the tumour hampers the effectiveness of immunotherapies. The ERC-funded project GLIOMERS is pioneering a localised, immunomodulatory polymeric drug delivery system designed to enhance GBM immunotherapy. Using a microfluidic-assisted method, the research team will develop hybrid nanocarriers combining hyaluronic acid for immunomodulation and poly-L-lysine for brain penetration. These carriers, conjugated with chemotherapeutics, aim to stimulate anti-tumour immunity and achieve local drug distribution. The GLIOMERS novel nanomedicine has the potential to improve T cell-mediated immune responses and therapeutic outcomes for GBM patients.

Objective

Research focusing on cancer immunotherapy has provided little progress toward improved survival rates for patients with glioblastoma (GBM), a poorly immunogenic tumor. Clinical trials for GBM immunotherapy primarily focus on the systemic administration of therapeutics; however, they have shown limited therapeutic success. The blood-brain barrier, the tumor immune microenvironment (TIME), the extracellular matrix, the highly invasive/proliferative nature of GBM, and intra- and inter-patient heterogeneity represent challenges to immunotherapy success. Administering polymer therapeutics as a class of biodegradable nanomedicines for localized treatment − a concept I pioneered − represents a less explored area that may fulfill the potential of GBM immunotherapy while reducing doses and adverse systemic effects.

GLIOMERS aims to design an immunomodulatory brain-penetrating polymeric drug delivery system that will exploit its intrinsic therapeutic effect by synergizing with conjugated chemotherapeutic agent(s) to directly stimulate antitumor immunity. By encompassing different biomaterials properties, hybrid nanocarriers will be developed using a synthetic microfluidic-assisted approach based on chemically stabilized self-assembled hyaluronic acid – as immunomodulator – with complementary poly-L-lysine to support brain penetration. I will capitalize on the properties of this new class of nanocarriers by conjugating chemotherapeutics re-purposed for immunotherapy. This approach will allow not only the local spread of the drug within the GBM, but also an additional rewiring of immunosuppressive TIME with an enhanced T cell-mediated immune response.

GLIOMERS will provide an innovative advance in the design of translational nanomedicines for local brain delivery, contributing to enhanced immunotherapeutic efficacy for GBM treatment.

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(opens in new window) ERC-2024-STG

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Host institution

UNIVERSITA DEGLI STUDI DI PADOVA
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.

€ 1 498 175,00
Address
VIA 8 FEBBRAIO 2
35122 PADOVA
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 498 175,00

Beneficiaries (1)

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