LB952 A phase 1 trial of DSG3-CAART cells in mucosal-dominant pemphigus vulgaris (mPV) patients: Preliminary data

Chang, D.J.; Basu, S.; Micheletti, Robert G.; Maverakis, E.; Marinkovich, M. Peter; Porter, D; Abedi, M.; Weng, Wen‐Kai; Hoffman, K.; Volkov, Jenell; Nunez, D.; Milone, M.C.; Binder, G.K.; Payne, Adam

doi:10.1016/j.jid.2022.05.971

Cited by 4 publications

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“…4a ). In preclinical studies of desmoglein 3 (DSG3)-CAART for the treatment of mucosal pemphigus vulgaris, similar induction of CAART proliferation and IFNγ production by soluble autoantibodies occurred 21 , 33 , although data from the first four cohorts in the ongoing DSG3-CAART clinical trial (NCT04422912) indicate no cytokine release syndrome or dose-limiting toxicities, as well as a dose-related increase in DSG3-CAART persistence throughout the 28 days following infusion 34 , suggesting that soluble autoantibodies do not mediate adverse events or prevent DSG3-CAART engraftment. Nevertheless, to mitigate risk, dose escalation is planned in the MuSK-CAART phase 1 clinical study design.…”

Section: Discussionmentioning

confidence: 99%

Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells

Mao

Vieira

et al. 2023

Nat Biotechnol

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Muscle-specific tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies that disrupt neuromuscular junction signaling. To avoid chronic immunosuppression from current therapies, we engineered T cells to express a MuSK chimeric autoantibody receptor with CD137-CD3ζ signaling domains (MuSK-CAART) for precision targeting of B cells expressing anti-MuSK autoantibodies. MuSK-CAART demonstrated similar efficacy as anti-CD19 chimeric antigen receptor T cells for depletion of anti-MuSK B cells and retained cytolytic activity in the presence of soluble anti-MuSK antibodies. In an experimental autoimmune MG mouse model, MuSK-CAART reduced anti-MuSK IgG without decreasing B cells or total IgG levels, reflecting MuSK-specific B cell depletion. Specific off-target interactions of MuSK-CAART were not identified in vivo, in primary human cell screens or by high-throughput human membrane proteome array. These data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG.

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Section: Discussionmentioning

confidence: 99%

Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells

Mao

Vieira

et al. 2023

Nat Biotechnol

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“…Chimeric autoantibody receptor (CAAR) T cells have been developed to target B cells bearing specific autoantibodies. One of the earliest examples was CAAR T cells targeting the pemphigus vulgaris autoantigen, desmoglein 3, 13 which has progressed to clinical trials 14 . In 2023, Oh et al 5 .…”

Section: Figurementioning

confidence: 99%