Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance
NCI - National Cancer Institute
About This Grant
Solid tumors may evade immune destruction due to T-cell or dendritic cell (DC) dysfunction, and current immunotherapies face limitations in solid tumors. This project addresses these challenges by leveraging our myeloid chimeric antigen receptor (CAR) expertise to mechanistically characterize a novel DC-based immunotherapy: αB7H3-TLR4 CAR-DCs. These engineered DCs express a B7H3-specific CAR fused to the intracellular signaling domain of Toll-like receptor 4 (TLR4). Preliminary data demonstrate that αB7H3-TLR4 CAR-DCs efficiently capture tumor antigens from tumor cells expressing the tumor associated antigen B7H3, potently upregulate costimulatory molecules, and robustly cross-prime naïve tumor-specific CD8⁺ T cells, leading to complete tumor rejection and durable immune memory in a heterogenous B7H3-expressing sarcoma model. This project will dissect the distinct roles of MyD88 and TRIF signaling pathways downstream of TLR4 in these CAR-DCs. Aim 1 will define the role of MyD88 in acute T-cell priming and effector differentiation, while Aim 2 will define the role of TRIF in long-term memory and recall responses. By elucidating these mechanisms, we will provide a roadmap for rationally designing DC-based therapies that maximize both immediate tumor control and durable immune protection, ultimately leading to more effective treatments for a wide range of solid tumors.
Grant Summary
Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance is a NCI - National Cancer Institute grant providing up to $400K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $400K
2028-04-30
- 1Confirm your organization is eligible for Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance 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.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance: Frequently Asked Questions
Who is eligible for the Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance?
Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance 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 Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance provide?
Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance provides up to $400K 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 Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance deadline?
Applications for Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance are due 2028-04-30 (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 Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance?
To apply for Harnessing TLR4 Signaling Pathways in CAR Dendritic Cells to Overcome Tumor Immune Tolerance, 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.