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Engineering Biomaterial-Based Dendritic Cell Therapies for Antigen-Specific Immune Tolerance

Award Number: R01AI192491
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Engineering Biomaterial-Based Dendritic Cell Therapies for Antigen-Specific Immune Tolerance - Project Summary: Engineering Biomaterial-Based Dendritic Cell Therapies for Antigen-Specific Immune Tolerance Loss of immune tolerance underlies autoimmune diseases and transplant rejection, yet existing immunotherapies are largely nonspecific and require chronic systemic immunosuppression. Dendritic cells (DCs) are uniquely positioned to restore antigen-specific tolerance by inducing regulatory T cells (Tregs); however, tolerogenic DCs (tolDCs) generated in vivo are typically short-lived and unstable. This project will engineer biomaterial formulations that 1) extend tolDC persistence to improve pTreg generation or 2) direct them toward lymph-node (LN) niches that favor durable Treg induction. In Aim 1, we will develop sustained-release microparticles (MPs) incorporating the push/pull immunomodulatory combination PPI9 (CEP-33779 + R848) to generate long-lived, potent tolDCs ex vivo. We will define optimal viability and tolerogenic marker expression and test whether PPI9-MP–treated tolDCs induce antigen-specific peripheral Tregs (pTregs) in vitro and in vivo, including CNS1-deficient mouse models that isolate pTreg function. An additional sub-aim will investigate an “off-the-shelf” allogeneic tolDC therapy using a combination of sustained PPI9 delivery and MHC I silencing. In Aim 2, we will optimize nanoparticle (NP) formulations that selectively target LN-resident DCs. Using charge- modulated and PEG-stabilized liposomes, we will identify parameters that maximize LN uptake and tolDC marker expression while maintaining efficient PPI9 loading. Top-performing candidates will advance to tolerance efficacy studies in the experimental autoimmune encephalomyelitis (EAE) models. Together, these studies will establish design rules linking tolDC persistence or LN targeting to pTreg induction. The results will enable next-generation, antigen-specific tolerance therapies with defined potency metrics and translatable manufacturing strategies for autoimmunity and transplantation.


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 = $584,755 )
2026	2026	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	8/18/2026	NEW	$584,755
														Subtotal = $584,755

Grand Total All Awards = $584,755

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Engineering Biomaterial-Based Dendritic Cell Therapies for Antigen-Specific Immune Tolerance

Award Number: R01AI192491

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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