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Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies

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收录情况： ◇ SCIE

作者：
Zhang Zheng[1,2,3] * ; Markmann Caroline[1,2] ; Yu Ming[4] ; Agarwal Divyansh[5] ; Rostami Susan[4] ; Wang Wei[4] ; Liu Chengyang[4] ; Zhao Huiwu[4] ; Ochoa Trini[1] ; Parvathaneni Kalpana[1,2] ; Xu Xiaoming[1,2] ; Li Eric[2] ; Gonzalez Vanessa[2] ; Khadka Roman[1,2] ; Hoffmann Jennifer[1,2] ; Knox James J[1] ; Scholler John[2] ; Marcellus Brooke[6] ; Allman David[1] ; Fraietta Joseph A[1,2,7] ; Samelson-Jones Benjamin[8] ; Milone Michael C[1,2] ; Monos Dimitri[6] ; Garfall Alfred L[9] ; Naji Ali[4] ; Bhoj Vijay G[1,2] ;
单位： [1]Department of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [2]Center for Cellular Immunotherapies, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [3]DepartmentofOrthopaedicSurgery,TongjiHospital,TongjiMedicalCollege,HuazhongUniversityofScience andTechnology,Wuhan,P.R.China [4]Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [5]Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA [6]Department of Pathology & Laboratory Medicine, Immunogenetics Laboratory, Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA [7]Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [8]Division of Hematology, Children’s Hospital of Philadelphia and University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [9]Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
出处：
DOI： 10.1016/j.xcrm.2023.101336
ISSN：

摘要：
Pre-existing anti-human leukocyte antigen (HLA) allo-antibodies constitute a major barrier to transplantation. Current desensitization approaches fail due to ineffective depletion of allo-specific memory B cells (Bmems) and long-lived plasma cells (LLPCs). We evaluate the efficacy of chimeric antigen receptor (CAR) T cells targeting CD19 and B cell maturation antigen (BCMA) to eliminate allo-antibodies in a skin pre-sensitized murine model of islet allo-transplantation. We find that treatment of allo-sensitized hosts with CAR T cells targeting Bmems and LLPCs eliminates donor-specific allo-antibodies (DSAs) and mitigates hyperacute rejection of subsequent islet allografts. We then assess the clinical efficacy of the CAR T therapy for desensitization in patients with multiple myeloma (MM) with pre-existing HLA allo-antibodies who were treated with the combination of CART-BCMA and CART-19 (ClinicalTrials.gov: NCT03549442) and observe clinically meaningful allo-antibody reduction. These findings provide logical rationale for clinical evaluation of CAR T-based immunotherapy in highly sensitized candidates to promote successful transplantation.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

基金：
The authors also thank the following funding sources: the National Blood Foundation (V.G.B.), the Burroughs Wellcome Fund (V.G.B.), NIH/NHLBI (R01 HL137335-01A1; V.G.B., B.S.-J., M.C.M.), and NIH/NIAID (U01 AI163087-01; V.G.B., A.N., A.L.G., M.C.M.).
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 2 区 细胞生物学
JCR分区：
出版当年[2021]版：
Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Department of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [2]Center for Cellular Immunotherapies, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [3]DepartmentofOrthopaedicSurgery,TongjiHospital,TongjiMedicalCollege,HuazhongUniversityofScience andTechnology,Wuhan,P.R.China
通讯作者：
通讯机构： [1]Department of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA [2]Center for Cellular Immunotherapies, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
推荐引用方式(GB/T 7714)：
Zhang Zheng,Markmann Caroline,Yu Ming,et al.Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies[J].CELL REPORTS MEDICINE.2023,4(12):101336.doi:10.1016/j.xcrm.2023.101336.
APA：
Zhang Zheng,Markmann Caroline,Yu Ming,Agarwal Divyansh,Rostami Susan...&Bhoj Vijay G.(2023).Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies.CELL REPORTS MEDICINE,4,(12)
MLA：
Zhang Zheng,et al."Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies".CELL REPORTS MEDICINE 4..12(2023):101336

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