Case study of CD19 CAR T therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis phase I/II trial.

Autor:	Volkov J; Cabaletta Bio, Philadelphia, PA, USA., Nunez D; Cabaletta Bio, Philadelphia, PA, USA., Mozaffar T; University of California Irvine School of Medicine, Department of Neurology, Irvine, CA, USA., Stadanlick J; Cabaletta Bio, Philadelphia, PA, USA., Werner M; Cabaletta Bio, Philadelphia, PA, USA., Vorndran Z; Cabaletta Bio, Philadelphia, PA, USA., Ellis A; Cabaletta Bio, Philadelphia, PA, USA., Williams J; Cabaletta Bio, Philadelphia, PA, USA., Cicarelli J; Cabaletta Bio, Philadelphia, PA, USA., Lam Q; Cabaletta Bio, Philadelphia, PA, USA., Furmanak T; Cabaletta Bio, Philadelphia, PA, USA., Schmitt C; Cabaletta Bio, Philadelphia, PA, USA., Hadi-Nezhad F; Cabaletta Bio, Philadelphia, PA, USA., Thompson D; Cabaletta Bio, Philadelphia, PA, USA., Miller C; Cabaletta Bio, Philadelphia, PA, USA., Little C; Cabaletta Bio, Philadelphia, PA, USA., Chang D; Cabaletta Bio, Philadelphia, PA, USA., Basu S; Cabaletta Bio, Philadelphia, PA, USA. Electronic address: samik.basu@cabalettabio.com.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Nov 06; Vol. 32 (11), pp. 3821-3828. Date of Electronic Publication: 2024 Sep 07.
DOI:	10.1016/j.ymthe.2024.09.009
Abstrakt:	Under compassionate use, chimeric antigen receptor (CAR) T cells have elicited durable remissions in patients with refractory idiopathic inflammatory myopathies (IIMs). Here, we report on the safety, efficacy, and correlative data of the first subject with the immune-mediated necrotizing myopathy (IMNM) subtype of IIM who received a fully human, 4-1BBz anti-CD19-CAR T cell therapy (CABA-201) in the RESET-Myositis phase I/II trial (NCT06154252). CABA-201 was well-tolerated following infusion. Notably, no evidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was observed. Creatine kinase levels decreased, and muscular strength improved post-infusion. Peripheral B cells were depleted rapidly following infusion, and the subject achieved peripheral B cell aplasia by day 15 post-infusion. Peripheral B cells returned at 2 months post-infusion and were almost entirely transitional. Autoantibodies to SRP-9, SRP-72, SRP-54, and Ro-52, decreased relative to baseline, whereas antibodies associated with pathogens and vaccinations remained stable. The infusion product consisted of predominantly CD4 + effector memory T cells and exhibited in vitro cytolytic activity. Post-infusion, CABA-201 expansion peaked at day 15 and was preceded by a serum IFN-γ peak on day 8 with peaks in serum IL-12p40 and IP-10 on day 15. These data detail the safety, efficacy, and pharmacodynamics of CABA-201 in the first IMNM subject. Competing Interests: Declaration of interests J.V., D.N., J.S., M.W., Z.V., A.E., J.W., J.C., Q.L., T.F., C.S., F.H.-N., D.T., C.M., C.L., D.C., and S.B. are employees of Cabaletta Bio. (Copyright © 2024 Cabaletta Bio. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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