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Engineered nanocarriers for simultaneous anticancer immune response and “switching” of tumor-associated macrophages for intranasal glioblastoma treatment

Project description

Immunotherapy for glioblastoma

Glioblastoma (GBM) remains a non-curable disease due to its high complexity and location beyond the blood-brain barrier complicating access by conventional therapies. The current treatment includes tumour resection followed by radiotherapy or chemotherapy with a survival rate less than 5 % five years post-diagnosis. Tumour-associated macrophages type 2 (M2 macrophages) comprise 30–50 % of the infiltrated cells in the GBM microenvironment and support tumour expansion. The EU-funded BraINstorm project aims to develop the stimulation of the immune system via the delivery of tumour antigen peptides and immunomodulatory oligonucleotides promoting the reprogramming of M2 macrophages into M1 macrophages with an anti-tumour effect.

Objective

Glioblastoma (GBM) remains a non-curable disease due to its high complexity and its position beyond the blood-brain barrier, which precludes access by conventional therapies. The current standard of care includes tumor resection surgery followed by radiotherapy or chemotherapy; an invasive process with a survival rate after five years is less than 5%. Tumor-associated macrophages (TAM) type 2 (M2 macrophages) comprise 30-50% of the infiltrated cells in GBM microenvironment and support tumor expansion. Immunotherapy represents an appealing strategy to treat several cancer types by turning the immune system against tumor cells; tumor antigen peptides (TAAs) recently emerged as an immunotherapeutic approach that can provide for a long-lasting immune response. Immunomodulatory oligonucleotides can “switch” M2 macrophages into M1 macrophages that produce an anti-tumoral effect. The BraINstorm (Brain INtranasal storm) project aims to engineer a hyaluronic acid (HA)-based combination conjugates that tackle GBM by the stimulation of the immune system via the delivery of TAAs and an immunomodulatory oligonucleotide (CpG) that promotes M2 macrophage “re-education” generating an “anticancer storm”. In parallel, taking advantage of the intrinsic muco-adhesivity of HA, BraINstorm will explore the nose-to-brain drug delivery, a more patient-friendly route that reduces the invasiveness. Novel combination immunoconjugates will be fully chemical-physical characterized and preliminary in vitro studies will be performed assessing the biocompatibility, drug release, and nasal mucosa barrier crossing in an ex-vivo model. Finally, the prophylactic and therapeutic activity of the HA-based conjugates will be in vivo explored in a clinically relevant GBM in vivo model through intranasal (IN) and local treatment administration with regards to effects on tumor size, immune memory, and survival.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITE CATHOLIQUE DE LOUVAIN
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.

€ 166 320,00
Address
PLACE DE L UNIVERSITE 1
1348 LOUVAIN LA NEUVE
Belgium

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Region
Région wallonne Prov. Brabant Wallon Arr. Nivelles
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.

€ 166 320,00
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