医学
CD19
细胞疗法
嵌合抗原受体
免疫学
细胞
癌症研究
T细胞
抗体
免疫系统
遗传学
生物
作者
C. Tur,Markus Eckstein,Joachim Velden,Simon Rauber,Christina Bergmann,Janina Auth,Laura Bucci,Giulia Corte,Melanie Hagen,Andreas Wirsching,Ricardo Grieshaber‐Bouyer,Petra Reis,Nicolai A. Kittan,Jochen Wacker,Aleix Rius Rigau,Andreas Ramming,Maria Antonietta D’Agostino,Arndt Hartmann,Fabian Müller,Andréas Mackensen,Aline Bözec,Georg Schett,Maria Gabriella Raimondo
标识
DOI:10.1136/ard-2024-226142
摘要
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.
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