The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization
NIBIB - National Institute of Biomedical Imaging and Bioengineering
About This Grant
PROJECT SUMMARY: There is a need for a new immune engineering platform technology to engineer T cell responses and direct their function for diseases spanning from viral infection to cancer. Most vaccination strategies rely on delivering the antigen of interest along with a variety of adjuvants to enhance the response. We have developed nanoparticles which deliver costimulatory molecules and proinflammatory cytokines to tumors that can function in an antigen agnostic manner to generate potent local and systemic immune responses. However, technologies capable of directly boosting antigen presentation to enhance viral and antitumor immunity are lacking. We have developed a library of biodegradable poly(beta-amino ester) (PBAE) nanoparticles (NPs) capable of delivering a variety of nucleic acid cargoes to specific cell types and identified initial formulations to specifically deliver genes to antigen presenting cells (APCs) and tumor cells. Here, we will develop novel antigen- presentation modulating (APM) NPs, enhancing MHC expression, and engendering vaccination strategies for broad applications to cancer, infectious disease, and autoimmunity. To develop these APM-NPs, we will systematically test whether NP-mediated delivery of plasmid DNAs encoding MHC transactivators and/or interferon pathway genes can enhance antigen presentation in tumor cells (Aim 1a) and TLR agonists, immunoproteosome components, costimulatory molecules, and transcription factors that polarize dendritic cells can improve antigen presentation in APCs (Aim 1b). To develop even more improved formulations specific for APCs and tumor cells, we will synthesize a library of biodegradable polymers based on linear, branched, and lipophilic PBAEs and screen the library for efficient cell type specific delivery (Aim 1c) and confirm efficiency and specificity in vivo (Aim 1d). Using our already identified formulations, we will combinatorially evaluate whether tumor- or APC-directed delivery or a combination can enhance antigen specific T cell responses in co-culture models in vitro (Aim 2a) and thereby identify the most promising candidates to evaluate in vivo. Using an adoptive transfer model to allow us to track antigen specific T cells, we will then evaluate the impact of optimized APM-NPs to modulate local and systemic antitumor immune responses using high dimensional flow cytometry and a novel multiplex immunofluorescence panel optimized for murine FFPE tissues (Aims 2b, 2c). Finally, to test whether the optimized combinatorial APM-NP approach can synergize with immunotherapy and lead to a therapeutic benefit, we will evaluate whether local delivery of APM-NPs, in combination with checkpoint inhibition, can treat two mouse models of cancer (Aim 2d). As this technology is fundamentally flexible, if successful, the proposal will lay the foundational groundwork for a novel platform technology to genetically modulate antigen presentation and enhance vaccination strategies, with applications to viral vaccination, cancer immunotherapy, and beyond.
Grant Summary
The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization is a NIBIB - National Institute of Biomedical Imaging and Bioengineering grant providing up to $599K for university, nonprofit, healthcare org. Applications are due 2029-05-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $599K
2029-05-31
- 1Confirm your organization is eligible for The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization from NIBIB - National Institute of Biomedical Imaging and Bioengineering, 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 NIBIB - National Institute of Biomedical Imaging and Bioengineering before the deadline.
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The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization: Frequently Asked Questions
Who is eligible for the The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization?
The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization is offered by NIBIB - National Institute of Biomedical Imaging and Bioengineering 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 The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization provide?
The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization provides up to $599K per award from NIBIB - National Institute of Biomedical Imaging and Bioengineering. 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 The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization deadline?
Applications for The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization are due 2029-05-31 (open). Because deadlines can change, verify the date with the funder, NIBIB - National Institute of Biomedical Imaging and Bioengineering, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization?
To apply for The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization, 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 NIBIB - National Institute of Biomedical Imaging and Bioengineering.