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The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization

Award Number: R21EB037272
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $598,859 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	5/22/2026	NEW	$598,859
														Subtotal = $598,859

Grand Total All Awards = $598,859

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The Development of antigent-presentation modulating nanoparticles (APM-NPs) to improve immunization

Award Number: R21EB037272

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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