CD19-CAR T-cell therapy induces deep tissue depletion of B cells

Tur C, Eckstein M, Velden J, Rauber S, Bergmann C, Auth J, Bucci L, Corte G, Hagen M, Wirsching A, Grieshaber Bouyer R, Reis P, Kittan N, Wacker J, Rigau AR, Ramming A, D’Agostino MA, Hartmann A, Müller F, Mackensen A, Bozec A, Schett G, Raimondo MG (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

Article Number: ard-2024-226142

DOI: 10.1136/ard-2024-226142

Abstract

Objectives CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo. Methods Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs. Results were compared with lymph node biopsies from rituximab (RTX)-treated AID patients with absence of peripheral B cells. Conventional and immunohistochemistry staining were performed on lymph node tissue to assess architecture as well the number of B cells, follicular dendritic cells (FDCs), plasma cells, T cells and macrophages. Results Sequential lymph node biopsies were analysed from five patients with AID before and after CD19-CAR T-cell therapy and from five patients with AID after RTX treatment. In addition, non-lymphoid organ biopsies (colon, kidney and gallbladder) from three additional patients with AID after CD19-CAR T-cell therapy were analysed. CD19+ and CD20+ B cells were completely depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells and macrophages in the lymph nodes remained unchanged. Follicular structures were disrupted and FDCs were depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX. Non-lymphoid organs were completely depleted of B cells. Discussion This study demonstrates complete B-cell depletion in secondary lymphoid tissues of patients with AIDs following CD19-CAR T-cell therapy combined with standard lymphodepleting therapy.

Authors with CRIS profile

Carlo Tur Department of Medicine 3 – Rheumatology and Immunology Markus Eckstein Institute of Pathology Joachim Velden Department of Nephropathology Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Christina Bergmann Department of Medicine 3 – Rheumatology and Immunology Janina Auth Department of Medicine 3 – Rheumatology and Immunology Laura Bucci Department of Medicine 3 – Rheumatology and Immunology Melanie Hagen Department of Medicine 3 – Rheumatology and Immunology Ricardo Grieshaber Bouyer Professur für Klinische Systemimmunologie Aleix Rius Rigau Department of Medicine 3 – Rheumatology and Immunology Andreas Ramming Professur für Immunologie der Organschädigung Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Fabian Müller Department of Medicine 5 – Haematology and Oncology Andreas Mackensen Lehrstuhl für Innere Medizin V Aline Bozec Professur für Experimentelle Immuntherapie Georg Schett Lehrstuhl für Innere Medizin III Maria Gabriella Raimondo Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Fondazione Policlinico Universitario Agostino Gemelli IRCCS IT Italy (IT)

How to cite

APA:

Tur, C., Eckstein, M., Velden, J., Rauber, S., Bergmann, C., Auth, J.,... Raimondo, M.G. (2024). CD19-CAR T-cell therapy induces deep tissue depletion of B cells. Annals of the Rheumatic Diseases. https://doi.org/10.1136/ard-2024-226142

MLA:

Tur, Carlo, et al. "CD19-CAR T-cell therapy induces deep tissue depletion of B cells." Annals of the Rheumatic Diseases (2024).

BibTeX: Download