Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses
About This Grant
Glioblastomas, the most aggressive primary brain tumors, are incurable, with a median survival of ~18 months. These tumors are “immunologically cold” due to their highly suppressive immune microenvironment, with low immune infiltration and low tumor neoantigens production. Therefore, they have a poor response to anti-glioma immune-mediated strategies. We hypothesize that both the infiltration of immune cells and anti-glioma immunity depend on the integrity of the extracellular matrix (ECM). We have previously demonstrated that downregulation of Collagen I from glioma cells disrupts tumor organization and malignity and increases immune cellular influx. These alterations on the tumor immune microenvironment and extracellular matrix led us to propose to elucidate whether collagen ECM disruption will increase the efficacy of immune-stimulatory gene therapy. Immune stimulatory gene therapy has been recently tested in a successful Phase I clinical trial (NCT01811992): the therapy increases tumor antigen release into the TME induced by Ad-HSV1-TK and conversion of the systemic prodrug ganciclovir into a cytotoxic purine analogue which induces DNA replication termination causing death of dividing glioma cells; Ad-Flt3L increases dendritic cells’ recruitment into the TME, this combination results in powerful anti-glioma immune responses. Our preliminary data suggest that disruption of the collagen ECM in combination with with gene therapy leads to increased long term survival: the mechanisms that mediate this enhanced therapeutic efficacy remain unknown. The overall objective of this proposal is to elucidate the mechanisms mediating immune infiltration and ECM disruption induced by collagen inhibition within the TME, and how this potentiates immune stimulatory gene therapy. Employing novel approaches based on bicompartmental protein nanoparticles (biSPNPs), and genetically engineered models of glioma, we will downregulate ECM organization which together with gene therapy will result in a novel efficacious glioma treatment. Our goal is to demonstrate that this translational therapy can turn gliomas’ cold immune tumor microenvironment into a hot immune microenvironment, with a high response to immune stimulatory gene therapy. 1
Grant Summary
Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses is a NCI - National Cancer Institute grant providing up to $572K for university, nonprofit, healthcare org. Applications are due 2031-06-30 (open). Check eligibility and apply with FindGrants.
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Up to $572K
2031-06-30
- 1Confirm your organization is eligible for Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses: Frequently Asked Questions
Who is eligible for the Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses?
Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses provide?
Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses provides up to $572K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses deadline?
Applications for Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses are due 2031-06-30 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses?
To apply for Disruption of Collagen Extracellular Matrix Potentiates Anti-Glioma Immune Responses, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.