Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients

Dingfelder J, Taubmann J, von Heydebrand F, Aigner M, Bergmann C, Knitza J, Park S, Cheng JK, Van Blarcom T, Schett G, Mackensen A, Lutzny-Geier G (2025)

Publication Type: Journal article

Publication year: 2025

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 26

Article Number: 467

Journal Issue: 2

DOI: 10.3390/ijms26020467

Abstract

Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs). CAR-mediated, CD19-specific activity of these cells was evaluated in vitro by assessing cytotoxicity, cytokine release, and proliferation assays in response to autologous CD19+ B-cells, the CD19+ NALM-6 B-cell line, or a CD19− U937 non-B-cell line as targets. The results demonstrated an increased proliferation of Hu19-CD828Z CAR T-cells and dose-dependent cytotoxicity against primary autologous and NALM-6 B-cells compared to non-transduced controls or co-cultures with non-B-cells. Notably, autoimmune-patient-derived CAR T-cells produced lower levels of inflammatory cytokines than healthy-donor-derived CAR T-cells in response to CD19+ B-cell targets. These data support the potential of Hu19-CD828Z and its therapeutic cell product KYV-101 as a therapeutic strategy to achieve deep B-cell depletion in SLE, IIM, and SSc patients, and highlights its promise for broader application in B-cell-driven autoimmune disorders.

Authors with CRIS profile

Janin Dingfelder Department of Medicine 5 – Haematology and Oncology Jule Taubmann Department of Medicine 3 – Rheumatology and Immunology Christina Bergmann Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Andreas Mackensen Lehrstuhl für Innere Medizin V Gloria Lutzny-Geier Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Kyverna Therapeutics, Inc. US United States (USA) (US) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE)

How to cite

APA:

Dingfelder, J., Taubmann, J., von Heydebrand, F., Aigner, M., Bergmann, C., Knitza, J.,... Lutzny-Geier, G. (2025). Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients. International Journal of Molecular Sciences, 26(2). https://doi.org/10.3390/ijms26020467

MLA:

Dingfelder, Janin, et al. "Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients." International Journal of Molecular Sciences 26.2 (2025).

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