ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia.
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 67 citations in OpenAlex.
- Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire.Nature communications · 2025Trial
- Mapping clinical CAR-T cells: insights from scRNA-seq.Trends in molecular medicine · 2026Review
- Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma.Blood neoplasia · 2026Article
- Diverse approaches and sources to derive antitumor T cell for liver cancer: a single-cell sequence based research.Hepatology international · 2025Article
- Single-cell transcriptomics identifies PDIA4 as a marker of progression and therapeutic vulnerability in multiple myeloma.Journal of translational medicine · 2025Article
- EnhancedScience advances · 2025Article
- CAR T cell persistence in cancer.Trends in cancer · 2025Review
- Targeting synergetic endothelial inflammation by inhibiting NFKB and JAK-STAT pathways.iScience · 2025Article
- Myeloma cell-intrinsic ANXA1 elevation and T cell dysfunction contribute to BCMA-negative relapse after CAR-T therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Two-stage CD8Nature communications · 2025Article
- Inferring disease progression stages in single-cell transcriptomics using a weakly supervised deep learning approach.Genome research · 2025Article
- Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy.Frontiers in immunology · 2025Review
- Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.Experimental hematology & oncology · 2024Review
- B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.EMBO molecular medicine · 2024Article
- Inhibition of CD38 enzymatic activity enhances CAR-T cell immune-therapeutic efficacy by repressing glycolytic metabolism.Cell reports. Medicine · 2024Article
- Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies.International journal of molecular sciences · 2024Review
- Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.Leukemia · 2024Article
- Single-cell genomics-based immune and disease monitoring in blood malignancies.Clinical hematology international · 2024Review
- Treatment of multiple myeloma: What is the impact on T-cell function?Therapeutic advances in hematology · 2024Review
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Authors and funding
23 authors at 4 institutions in 3 countries.
Xue LiBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Xin GuoBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Yuqing ZhuInstitute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China; The First Hospital & Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China.
Guoqing WeiBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China.
Yanlei ZhangShanghai YaKe Biotechnology Ltd., Shanghai 200090, China.
Xia LiBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Huijun XuBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Jiazhen CuiBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Wenjun WuBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China.
Jingsong HeBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China.
Matthew E RitchieEpigenetics and Development Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia; School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC 3010, Australia.
Taylor M WeiskittelCenter for Individualized Medicine, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Hu LiCenter for Individualized Medicine, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Hua YuInstitute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China; The First Hospital & Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China.
Lijuan DingBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Mi ShaoBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Qian LuoBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Xiaoxiao XuBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Xinyi TengBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China.
Alex H ChangShanghai YaKe Biotechnology Ltd., Shanghai 200090, China.
Jin ZhangInstitute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China; The First Hospital & Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address: zhgene@zju.edu.cn.
He HuangBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China. Electronic address: huanghe@zju.edu.cn.
Yongxian HuBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China. Electronic address: 1313016@zju.edu.cn.
Zhejiang University · CNZhejiang Lab · CNMayo Clinic · USWalter and Eliza Hall Institute of Medical Research · AU
Funding
Predoctoral Training Program in Molecular PharmacologyT32GM072474 · NIGMS · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2005 to 2020
$2.4MNIGMS NIH HHS T32 GM072474
Abstract
Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored. Here, we longitudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajectory. Moreover, re-analysis of a single cell study from CD8
Indexed as
Immunotherapy, AdoptiveTranscriptomeAntigens, CD19B-Cell Maturation AntigenDrug Resistance, NeoplasmGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansLeukemia, Plasma CellReceptors, Antigen, T-CellRecurrenceSingle-Cell AnalysisT-LymphocytesTreatment OutcomeAntigens, CD19B-Cell Maturation AntigenReceptors, Antigen, T-Cellchimeric antigen receptor T cellplasma cell leukemiasingle-cell RNA sequencing
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