决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD19 CAR-T 细胞治疗后的侵袭性淋巴瘤
英文原题：Aggressive Lymphoma after CD19 CAR T-Cell Therapy.
查看英文原题
Aggressive Lymphoma after CD19 CAR T-Cell Therapy.
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中文摘要
一名复发性原发性中枢神经系统淋巴瘤患者接受替沙格列赛治疗后1个月，发生致命性、克隆性、自主增殖的CD4-CD8-CAR+外周T细胞淋巴瘤（PTCL）。PTCL具有克隆性T细胞受体重排；该重排在CAR-T 细胞制备所用单采产品中已可检测到，在自体移植前7个月的样本中也已存在。PTCL、用于CAR-T 细胞制备的单采样本以及自体移植样本中，均检测到CD34+干细胞及其后代细胞中的体细胞DNMT3A和TET2突变。PTCL还携带一项额外的体细胞TET2突变，该突变在CAR-T 细胞单采产品及最终CAR-T 细胞产品中均已以极低频率检出，提示克隆性造血参与了淋巴瘤发生。
展开英文摘要原文
The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation.
Somatic DNMT3A and TET2 mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant. The PTCL harbored an additional somatic TET2 mutation, which was already detectable in the CAR T-cell apheresis product and the final CAR T-cell product at very low frequencies, providing evidence that clonal hematopoiesis had contributed to lymphomagenesis.
论文信息
- 作者
- Kobbe G、Brüggemann M、Baermann BN、Wiegand L、Trautmann H、Yousefian S、Libertini S、Menssen HD
- 单位
- From the Department of Hematology, Oncology and Clinical Immunology (G.K., B.-N.B., P.-M.B., N.L., A.R., M. Seifert, C.S., U.G., R.-P.C., K.N., P.J., T.U., S.D.), the Institute of Pathology (M. Seidel, I.E.), the Institute for Transplantation Diagnostics and Cellular Therapy (J.C.F., J.M.R.), the Departments of Nuclear Medicine (F.G.), Rheumatology (J.H.W.D.), and Neurology (S.G.M.), and the Hiller Research Center (J.H.W.D.), University Hospital Düsseldorf, the Center for Integrated Oncology, Aachen-Bonn-Cologne-Düsseldorf (G.K., B.-N.B., P.-M.B., N.L., A.R., M. Seifert, C.S., U.G., R.-P.C., K.N., P.J., T.U., S.D.), and the Department of Diagnostic and Interventional Radiology, University Düsseldorf (G.A.), Düsseldorf, Medical Department II, Hematology and Oncology (M.B., H.T.), and the Department of Pathology (I.I.), University Medical Center Schleswig-Holstein, Kiel, the Department of Hematology, Oncology and Cancer Immunology, Campus Virchow, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin (L.W., F.D.), Berlin Institute of Health, Charité Universitätsmedizin Berlin (S.Y., S.H.), and Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (S.Y., S.H.), Berlin, the Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases Heidelberg (N.P.), the Innovation and Service Unit for Bioinformatics and Precision Medicine (D.H.), German Cancer Research Center, the European Molecular Biology Laboratory, Molecular Medicine Partnership Unit (D.F.), German Cancer Consortium (D.H., S.H., F.D.), the Pattern Recognition and Digital Medicine Group, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (D.H.), the Medical Faculty of Heidelberg (J.L.) and the Department of Medicine V (S.D.), Heidelberg University, German Cancer Consortium, partner site Berlin, and German Cancer Research Center (S.H., F.D.), Heidelberg, the Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen (R.K.), and the Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen (M.J.) - all in Germany; and Biomedical Research, Novartis (S.L., P.U.), and Novartis Pharma (H.D.M., H.J.M., J.G.) - both in Basel, Switzerland.Germany
- 文献类型
- 病例报告
- 期刊
- The New England journal of medicine2024 Oct 3
- 原文标识
- PubMed 39589371 · DOI 10.1056/NEJMoa2402730