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Developing non-immunosuppressive immune-based therapeutics for targeted treatment of autoimmune diseases

Award Number: R01AI165666
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: 08/24/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Developing non-immunosuppressive immune-based therapeutics for targeted treatment of autoimmune diseases - Project Summary Pemphigus vulgaris is a devastating B-cell mediated autoimmune disease. Autoantibodies produced by B cells targeting desmoglein-3 (Dsg3), a desmosomal protein, critical for intercellular adhesion, is responsible for the mucosal-dominant type of the disease and cause painful deep erosions in the mucosa. Anti-Dsg3 autoantibodies result in the disruption of the keratinocytes' connections, and, thereby, cause the formation of blisters and erosions. The direct pathogenic role of anti-Dsg3 autoantibodies in PV has been established. Monovalent antibodies have been shown to be sufficient to result in the formation of blisters. Standard treatments include immunosuppressive drugs that globally suppress the immune system. The goal of this project is to develop novel, targeted, immuno-therapeutic approaches to specifically and precisely target and deplete autoreactive B cells recognizing Dsg3. Established Dsg3 specific autoreactive B cells are used to optimize these methods. We will determine the efficacy and specificity of the approach using peripheral blood mononuclear cells (PBMCs) obtained from PV patients in different phases of the disease, including treatment- naive and relapse, and in vivo mouse models of the disease. Successful completion of this study will help translate the methods into a preclinical and, eventually, a clinical setting. The ease of production, low cost, compared to cell-based targeted approaches, and the lack of off-target side-effects compared to the existing treatments for PV make the proposed therapeutics breakthrough treatment options. Furthermore, the technology developed here can have wider applications to all autoantibody-driven diseases by directly targeting autoreactive cells without causing global immunosuppression.


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: 2025 ( Subtotal = $663,019 )
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	7/7/2025	NON-COMPETING CONTINUATION	$663,019
														Subtotal = $663,019

Issue Date FY: 2024 ( Subtotal = $664,312 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	2	7/17/2024	NON-COMPETING CONTINUATION	$664,312
2024	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	5/6/2024	NEW	$0
														Subtotal = $664,312

Issue Date FY: 2023 ( Subtotal = $700,726 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	8/24/2023	NEW	$700,726
														Subtotal = $700,726

Grand Total All Awards = $2,028,057

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Developing non-immunosuppressive immune-based therapeutics for targeted treatment of autoimmune diseases

Award Number: R01AI165666

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: 08/24/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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