ArticleCell2020
Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies.
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Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 284 papers, 5 of them syntheses that pooled it.
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284citing papers in PubMed, 5 pooled it
24.2field-weighted citation impact, top 1% of its field
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Who cites it
284 citing papers in PubMed, 5 syntheses or guidelines pooled it, 446 citations in OpenAlex.
- Safety and efficacy of CAR T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- Guillain-Barre syndrome in patients receiving chimeric antigen receptor T-cell therapy: an individual participant data meta-analysis.Frontiers in neurology · 2025Pooled it
- Neuropsychiatric manifestations following chimeric antigen receptor T cell therapy for cancer: a systematic review of clinical outcomes and management strategies.Journal for immunotherapy of cancer · 2024Pooled it
- Incidence of immune effector cell-associated neurotoxicity among patients treated with CAR T-cell therapy for hematologic malignancies: systematic review and meta-analysis.Frontiers in neurology · 2024Pooled it
- 2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma.Cancer biology & medicine · 2023Guideline
- Markedly Delayed Onset ICANS in the Setting of CAR T-Cell-Mediated Aseptic Meningoencephalitis: Two Cases.The Neurohospitalist · 2026Article
- LAIR1 suppresses phagocytosis via SHP2/USP22-mediated MYH9 degradation in glioma-associated microglia/macrophages to drive immunosuppression.British journal of cancer · 2026Article
- Real-World Experience With a ZUMA-1 Cohort 4 Adopted Approach to CRS and ICANS in CAR-T Recipients.European journal of haematology · 2026Article
- Data-centric feedback loops for next-generation immunotherapy development.Nature biomedical engineering · 2026Review
- Persistent parkinsonism with dopaminergic denervation following axicabtagene ciloleucel therapy for diffuse large B cell lymphoma: a case report.International journal of hematology · 2026Article
- Brain barriers at the crossroads of glioma immune surveillance and immunotherapy response.Nature reviews. Cancer · 2026Review
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Anti-CD19 CAR T Cells in Autoimmune Encephalitis: Inflammation Controlled, Neurodegeneration Unchecked?Annals of clinical and translational neurology · 2026Article
- Mania and psychosis following chimeric antigen receptor T-cell therapy: A report of two cases and mechanistic discussion.Brain, behavior, & immunity - health · 2026Article
- Advances and challenges in CAR-T cell therapy for breast cancer: from molecular design to clinical application.Cancer causes & control : CCC · 2026Review
- CAR T cells for pediatric CNS tumors: Clinical experience and reverse translational opportunities.Molecular therapy. Oncology · 2026Review
- Tumor-targeted bispecific antibodies effectively inhibit oncogenic pathways while minimizing toxicity.Science advances · 2026Article
- Review
- A Novel Strategy to Produce CAR-γδ T Cells via Site-Directed Gene Integration by a Combination of CRISPR/Cas9 and AAV.Cancer medicine · 2026Article
- Roads and detours for CAR T cell therapy in autoimmune diseases.Nature reviews. Drug discovery · 2026Review
224 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 3 countries.
Kevin R ParkerCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA.
Denis MiglioriniParker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Translational Research in Onco-Hematology and Department of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address: denis.migliorini@hcuge.ch.
Eric PerkeyGraduate Program in Cellular and Molecular Biology and Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, USA; Division of Hematology-Oncology, Department of Medicine and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kathryn E YostCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA.
Aparna BhaduriDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Puneet BaggaDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mohammad HarisDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Functional and Molecular Imaging Laboratory, Research Branch, Sidra Medicine, Doha, Qatar; Laboratory Animal Research Center, Qatar University, Doha, Qatar.
Neil E WilsonDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Fang LiuCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Khatuna GabuniaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John SchollerCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Thomas J MontineDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Vijay G BhojCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ravinder ReddyDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Suyash MohanDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ivan MaillardDivision of Hematology-Oncology, Department of Medicine and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Arnold R KriegsteinDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Carl H JuneParker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Avery D PoseyParker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Ansuman T SatpathyParker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: satpathy@stanford.edu.
University of Pennsylvania · USParker Institute for Cancer Immunotherapy · USCancer Research Institute · USUniversity of California, San Francisco · USHoward Hughes Medical Institute · USQatar Airways (Qatar) · QAStanford University · USUniversity of Geneva · CH
Funding
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MUdall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3MSpecial EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2MCenter for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8MTraining and DisseminationP41EB015893 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI REDDY, RAVINDER · 2012 to 2019
$11.3MStatistical atlases of brain tumor MRI:do imaging phenotypes predict progression?R01NS042645 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2002 to 2024
$8.7MDevelopment and Expansion of the Human Cerebral CortexR35NS097305 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD · 2017 to 2024
$8.5MLncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4MNotch Signaling in AlloimmunityR01AI091627 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PEAR, WARREN S · 2011 to 2025
$6.0MMapping the Developing Human Neocortex by Massively Parallel Single Cell AnalysisU01MH105989 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD · 2014 to 2016
$5.1MSingle cell epigenomics in cancer immunity and immunotherapyK08CA230188 · NCI · STANFORD UNIVERSITY · PI SATPATHY, ANSUMAN · 2018 to 2020
$448kEngineered T Cells Targeting Abnormal Glycans in Metastatic Prostate CancerIK2BX004183 · VA · PHILADELPHIA VA MEDICAL CENTER · PI POSEY, AVERY D. · 2018 to 2022
–BLRD VA IK2 BX004183Howard Hughes Medical InstituteNCI NIH HHS K08 CA230188NCI NIH HHS R35 CA209919NHGRI NIH HHS P50 HG007735NHGRI NIH HHS RM1 HG007735NIAID NIH HHS R01 AI091627NIBIB NIH HHS P41 EB015893NIGMS NIH HHS T32 GM007863NIMH NIH HHS U01 MH105989NINDS NIH HHS P50 NS062684NINDS NIH HHS R01 NS042645NINDS NIH HHS R35 NS097305
Abstract
CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity. A subset of patients treated with chimeric antigen receptor (CAR) T cells or bispecific T cell engager (BiTE) antibodies display severe neurotoxicity, including fatal cerebral edema associated with T cell infiltration into the brain. Here, we report that mural cells, which surround the endothelium and are critical for blood-brain-barrier integrity, express CD19. We identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm perivascular staining at the protein level. CD19 expression in the brain begins early in development alongside the emergence of mural cell lineages and persists throughout adulthood across brain regions. Mouse mural cells demonstrate lower levels of Cd19 expression, suggesting limitations in preclinical animal models of neurotoxicity. These data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.
Indexed as
AnimalsAntibodies, BispecificAntigens, CD19Blood-Brain BarrierB-LymphocytesBrainCell Line, TumorCytotoxicity, ImmunologicEpithelial CellsHumansImmunotherapyImmunotherapy, AdoptiveMiceMice, Inbred NODMice, SCIDMuscle, Smooth, VascularAntibodies, BispecificAntigens, CD19Receptors, Antigen, T-CellReceptors, Chimeric Antigen
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