Summary
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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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/887609 |
| Start date: | 01-09-2020 |
| End date: | 31-08-2022 |
| Total budget - Public funding: | 166 320,00 Euro - 166 320,00 Euro |
Cordis data
Original description
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.Status
CLOSEDCall topic
MSCA-IF-2019Update Date
28-04-2024
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