Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus

Kretschmann S, Völkl S, Reimann H, Krönke G, Schett G, Achenbach S, Lutzny-Geier G, Müller F, Mougiakakos D, Dingfelder J, Flamann C, Hanssens L, Gary R, Mackensen A, Aigner M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Transplantation and Cellular Therapy Elsevier

DOI: 10.1016/j.jtct.2022.10.004

Abstract

Although it has been shown that the production of functional chimeric antigen receptor T cells is feasible in patients with B-cell malignancies, it is currently unclear whether sufficient amounts of functional autologous CAR T cells can be generated from patients with autoimmune diseases. Intrinsic T-cell abnormalities and T-cell–targeted immune suppression in patients with autoimmunity may hamper the retrieval of sufficient T cells and their transduction and expansion into CAR T cells. Patients with active systemic lupus erythematosus (SLE) underwent leukapheresis after tapering glucocorticoids and stopping T-cell–suppressive drugs. This material was used as source for manufacturing anti-CD19 CAR T-cell products (CAR) in clinical scale. Cells were transduced with a lentiviral anti-CD19 CAR vector and expanded under good manufacturing practice (GMP) conditions using a closed, semi-automatic system. Functionality of these CAR T cells derived from autoimmune patient cells was tested in vitro. Six SLE patients were analyzed. Leukapheresis could be successfully performed in all patients yielding sufficient T-cell numbers for clinical scale CAR T-cell production. In addition, CAR T cells showed high expansion rates and viability, leading to CAR T cells in sufficient doses and quality for clinical use. CAR T cells from all patients showed specific cytotoxicity against CD19+ cell lines in vitro. GMP grade generation of CD19 CAR T-cell products suitable for clinical use is feasible in patients with autoimmune disease.

Authors with CRIS profile

Simon Völkl Department of Medicine 5 – Haematology and Oncology Hannah Reimann Department of Medicine 5 – Haematology and Oncology Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Susanne Achenbach Department of Transfusion Medicine and Haemostaseology Gloria Lutzny-Geier Department of Medicine 5 – Haematology and Oncology Fabian Müller Department of Medicine 5 – Haematology and Oncology Dimitrios Mougiakakos Medizinische Fakultät Janin Dingfelder Department of Medicine 5 – Haematology and Oncology Cindy Flamann Department of Medicine 5 – Haematology and Oncology Andreas Mackensen Lehrstuhl für Innere Medizin V

Involved external institutions

Miltenyi Biotec GmbH DE Germany (DE)

How to cite

APA:

Kretschmann, S., Völkl, S., Reimann, H., Krönke, G., Schett, G., Achenbach, S.,... Aigner, M. (2022). Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus. Transplantation and Cellular Therapy. https://doi.org/10.1016/j.jtct.2022.10.004

MLA:

Kretschmann, S., et al. "Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus." Transplantation and Cellular Therapy (2022).

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