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Tolerogenic Dendritic Cell Membrane-Coated Nanoparticles for Precision Multiple Sclerosis Therapy

Award Number: R21AI196694
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/20/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Tolerogenic Dendritic Cell Membrane-Coated Nanoparticles for Precision Multiple Sclerosis Therapy - Project Summary Multiple sclerosis (MS) is an autoimmune disease that targets myelin, leading to neurological disability and chronic symptoms. Nearly 1 million people in the U.S. are affected. The total MS-related annual economic cost has reached $85.4 billion. Current treatments focus on symptom management and broadly suppress the immune system, which compromises protective immunity and fails to provide long-term relief. There is an urgent unmet clinical need for safe and effective treatment strategy for MS. MS pathology is driven by autoreactive CD4+ T cells. Th1 and Th17 cells can infiltrate the central nervous system (CNS) and cause inflammation after reactivation. Follicular T helper cells also contribute to MS pathology by promoting autoantibody production. The persistent inflammation impairs regulatory T cell function and hinders nerve tissue regeneration. Leveraging the cognate interaction between peptide major histocompatibility complex class II (pMHCII) and T-cell receptor (TCR) can selectively engage autoreactive T cells for suppression. However, the heterogeneity of MS and the diversity of T-cell clones and patient MHC haplotypes make targeted drug delivery challenging. The blood-brain barrier further complicates treatment delivery. Tolerogenic DCs (tolDCs) can suppress antigen-specific T-cell function through inhibitory surface proteins, including programmed death-ligand 1 and 2 (PD-L1/2) and Fas ligand (FasL). Mimicing the tolDC/T-cell interaction can potentially advance antigen-specific MS treatment. Our long-term goal is to develop a generalizable personalized treatment strategy that can selectively suppress autoantigen-specific T cells for MS treatment. The objective of this project is to develop protein-decorated rapamycin-encapsulated nanoparticles to selectively suppress CNS-infiltrated autoantigen-specific CD4+ T cells. We hypothesize that our proposed nanoparticle design can mediate selective suppression of antigen-specific CD4+ T cells. We also propose to promote nanoparticles brain accumulation to selectively suppress CNS-infiltrated autoantigen-specific CD4+ T cells. To test this hypothesis, we propose the following two specific aims: (1) developing protein-decorated nanoparticles for antigen-specific T-cell-targeted delivery and (2) determining their brain entry and therapeutic effects in models of MS. We expect to establish a proof-of-concept for a personalized antigen-specific T-cell- targeted drug delivery platform, leading to new CNS-targeted MS treatments and advancing understanding of T cell regulation in autoimmunity.


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 = $137,429 )
2026	2026	SYRACUSE UNIVERSITY	900 S CROUSE AVE	SYRACUSE	NY	13244	ONONDAGA	USA	Allergy and Infectious Diseases Research	000	1	4/21/2026	NEW	$137,429
														Subtotal = $137,429

Grand Total All Awards = $137,429

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Tolerogenic Dendritic Cell Membrane-Coated Nanoparticles for Precision Multiple Sclerosis Therapy

Award Number: R21AI196694

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/20/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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