0434 Clinical and translational data from a first-in-human study of a novel precision cellular immunotherapy (DSG3-CAART) in mucosal pemphigus vulgaris

A.S. Payne; D. Nunez; J. Volkov; D. Thompson; M. Werner; J. Stadanlick; L. Ishikawa; J. Cicarelli; Q. Lam; C. Miller; K. Sheipe; S. Vieira; D. Porter; R. Micheletti; E. Maverakis; M. Abedi; J.A. Fairley; U. Farooq; M. Marinkovich; W. Weng; A. Dominguez; O. Pacha; A. Zhou; J. Mehta; M. Shinohara; D. Maloney; M. Milone; G. Binder; D. Chang; S. Basu

doi:10.1016/j.jid.2025.06.439

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0434 Clinical and translational data from a first-in-human study of a novel precision cellular immunotherapy (DSG3-CAART) in mucosal pemphigus vulgaris

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0434 Clinical and translational data from a first-in-human study of a novel precision cellular immunotherapy (DSG3-CAART) in mucosal pemphigus vulgaris

A.S. Payne, D. Nunez, J. Volkov, D. Thompson, M. Werner, J. Stadanlick, L. Ishikawa, J. Cicarelli, Q. Lam, C. Miller, …

Journal of investigative dermatology, Vol.145(8 Suppl), pp.S75-S75

08/2025

DOI: 10.1016/j.jid.2025.06.439

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Abstract

Mucosal pemphigus vulgaris (mPV) is an autoimmune disease caused by autoantibodies to the epithelial adhesion protein desmoglein 3 (DSG3). As a precision medicine approach for mPV, chimeric autoantibody receptor T cell (CAART) technology was developed using an autoantigen-based synthetic immunoreceptor designed to direct T cell cytotoxicity only against anti-DSG3 autoantibody-expressing B cells to avoid global B cell depletion. 23 mPV subjects were enrolled in an open-label phase 1 study of DSG3-CAART, employing 6 dose-escalation cohorts without preconditioning plus 2 cohorts with preconditioning. One subject experienced grade 1 cytokine release syndrome. No dose-limiting toxicities occurred. DSG3-CAART persistence increased linearly across the first 4 cohorts then plateaued; preconditioning with IVIg, cyclophosphamide, +/- fludarabine did not increase post-infusion persistence. After infusion, a decrease in CAAR mean fluorescence intensity was observed in all subjects, associated with enrichment of stem cell memory-like immunophenotypes, little to no IFN-gamma secretion, and no consistent pattern of improvement in clinical disease activity scores or anti-DSG3 antibody titers. In cytotoxicity assays, CAARTs with low CAAR expression demonstrated inferior cytolytic activity compared to those with high CAAR expression. Collectively, these first-in-human data indicate DSG3-CAART is well tolerated, but suggest low CAAR expression post-infusion, potentially due to soluble antibody internalization or inhibition, may impact clinical efficacy.

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Title: Subtitle: 0434 Clinical and translational data from a first-in-human study of a novel precision cellular immunotherapy (DSG3-CAART) in mucosal pemphigus vulgaris
Creators: A.S. Payne - Columbia University
D. Nunez
J. Volkov
D. Thompson
M. Werner
J. Stadanlick
L. Ishikawa
J. Cicarelli
Q. Lam
C. Miller
K. Sheipe
S. Vieira - University of Pennsylvania
D. Porter - University of Pennsylvania
R. Micheletti - University of Pennsylvania
E. Maverakis - University of California, Davis
M. Abedi - University of California, Davis
J.A. Fairley - University of Iowa
U. Farooq - Univ of Iowa, Iowa City, Iowa, United States
M. Marinkovich - Stanford University
W. Weng - Stanford University
A. Dominguez - The University of Texas Southwestern Medical Center
O. Pacha - MD Anderson Cancer Center, Houston, Texas, United States
A. Zhou - Northwestern University
J. Mehta - Northwestern University
M. Shinohara - University of Washington
D. Maloney - University of Washington
M. Milone - University of Pennsylvania
G. Binder
D. Chang
S. Basu
Resource Type: Abstract
Publication Details: Journal of investigative dermatology, Vol.145(8 Suppl), pp.S75-S75
DOI: 10.1016/j.jid.2025.06.439
ISSN: 0022-202X
Publisher: Elsevier Inc
Language: English
Date published: 08/2025
Academic Unit: Dermatology
Record Identifier: 9984865310202771

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