Fully Human Anti-CD19 CAR T Cells Derived from Systemic Lupus Erythematosus Patients Exhibit Cytotoxicity with Reduced Inflammatory Cytokine Production

Dingfelder J, Aigner M, Taubmann J, Minopoulou I, Park S, Kaplan CD, Cheng JK, Van Blarcom T, Schett G, Mackensen A, Lutzny-Geier G (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Transplantation and Cellular Therapy Elsevier

DOI: 10.1016/j.jtct.2024.03.023

Abstract

KYV-101 is an autologous anti-CD19 chimeric antigen receptor (CAR)-T cell therapy under investigation for patients with B-cell driven autoimmune diseases. Hu19-CD828Z is a fully human anti-CD19 CAR designed and demonstrated to have a favorable clinical safety profile. Since anti-CD19 CAR T cells target and kill B cells in both circulation and tissues, the treatment with Hu19-CD828Z CAR T cells offers great potential in depleting autoreactive B cells. Demonstrate that Hu19-CD828Z CAR T cells manufactured from cryopreserved leukaphereses from patients with systemic lupus erythematosus (SLE) exhibit CAR-mediated and CD19-dependent cytokine release, proliferation and cytotoxicity when co-cultured with autologous primary B cells. T cells were enriched from cryopreserved leukaphereses from SLE patients or healthy donors (HD). CAR T cells were generated by transducing these cells with a lentiviral vector encoding Hu19-CD828Z. CAR-mediated and CD19-dependent activity was monitored in vitro in a set of cytotoxicity, cytokine release, and proliferation studies, in response to autologous primary CD19+ B cells, a CD19+ cell line (NALM-6), or a CD19− cell line (U937). Hu19-CD828Z CAR T cells produced from SLE patients or HD induced greater proliferation and dose-dependent cytotoxicity against both autologous primary B cells and the CD19+ NALM-6 cells than nontransduced control T cells or co-cultures with a CD19− cell line. Interestingly, there was lower inflammatory cytokine production from SLE patient-derived CAR T cells compared to HD donor-derived CAR T cells with either CD19+ cells or primary B cells. Hu19-CD828Z CAR T cells generated from SLE patient lymphocytes demonstrate CAR-mediated and CD19-dependent activity against autologous primary B cells with reduced inflammatory cytokine production supporting KYV-101 as a novel potential therapy for the depletion of pathogenic B cells in SLE patients.

Authors with CRIS profile

Janin Dingfelder Department of Medicine 5 – Haematology and Oncology Jule Taubmann Department of Medicine 3 – Rheumatology and Immunology Ioanna Minopoulou 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)

How to cite

APA:

Dingfelder, J., Aigner, M., Taubmann, J., Minopoulou, I., Park, S., Kaplan, C.D.,... Lutzny-Geier, G. (2024). Fully Human Anti-CD19 CAR T Cells Derived from Systemic Lupus Erythematosus Patients Exhibit Cytotoxicity with Reduced Inflammatory Cytokine Production. Transplantation and Cellular Therapy. https://doi.org/10.1016/j.jtct.2024.03.023

MLA:

Dingfelder, Janin, et al. "Fully Human Anti-CD19 CAR T Cells Derived from Systemic Lupus Erythematosus Patients Exhibit Cytotoxicity with Reduced Inflammatory Cytokine Production." Transplantation and Cellular Therapy (2024).

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