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CD19-CAR T-cell therapy induces deep tissue depletion of B cells
Carlo Tur (Università Cattolica del Sacro Cuore, Friedrich-Alexander-Universität Erlangen-Nürnberg), Markus Eckstein (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Joachim Velden (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Simon Rauber (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Christina Bergmann (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Janina Auth (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Laura Bucci (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Giulia Corte (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Melanie Hagen (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Andreas Wirsching (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Ricardo Grieshaber‐Bouyer (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Petra Reis (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Nicolai A. Kittan (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Jochen Wacker (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Aleix Rius Rigau (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Andreas Ramming (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Maria Antonietta D’Agostino (Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic), Arndt Hartmann (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Fabian Müller (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Andréas Mackensen (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Aline Bözec (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen), Georg Andreas Schett (Università Cattolica del Sacro Cuore, Friedrich-Alexander-Universität Erlangen-Nürnberg), Maria Gabriella Raimondo (Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen)
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.