ArticleNature medicine2021
Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells.
Open access · greenAbstract readClinical Trial, Phase I
In one paragraph
Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 2 pooled it
12.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- CAR T-cell therapy in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.Bone marrow transplantation · 2026Pooled it
- A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells.Frontiers in immunology · 2023Pooled it
- Fine-tuning affinity and spacer design enhances T cell potency in DLL3 and BCMA CAR T cells.mAbs · 2026Article
- Development of chimeric antigen receptors targeting the γδ T cell receptor.Molecular therapy. Oncology · 2026Article
- Metabolic profiling of CAR T-cells in patients reveals a shift toward amino acid-supported OXPHOS and informs transporter engineering.Research square · 2026Article
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Single-cell genomics links targeted functional manipulations to efficacy-associated chromatin signatures in CAR T cells.Research square · 2026Article
- Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.Cell · 2026Article
- Differential cytokine architecture in patients treated with CART19 versus CART22.Journal for immunotherapy of cancer · 2026Article
- Humanized and Charge-Optimized CSPG4-Specific CAR-T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Impact of Glycine-Serine Linker on Target Antigen Binding and Subsequent CD37CAR-T Performance.International journal of molecular sciences · 2026Article
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- Predictive biomarkers of response to chimeric antigen receptor (CAR) T-cell therapy for pan-haematologic cancer.Nature biomedical engineering · 2026Article
- Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Dynamic regulation of BACH2 enhances CAR T cell function.Molecular therapy. Oncology · 2026Article
- Ten-year experience of CD22 CAR T cells for children and young adults with B-cell acute lymphoblastic leukemia.Blood advances · 2026Article
- BACH2 regulates T cell lineage state to enhance CAR T cell function.Nature immunology · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Preclinical development of mesothelin-targeting CAR T cells for the treatment of cholangiocarcinoma.Hepatology communications · 2026Article
- Early cytokine and chemokine signals shape the anti-AML activity of bispecific engager-secreting T cells.Haematologica · 2026Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
36 authors at 9 institutions in 2 countries.
Nathan Singh *Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. nathan.singh@wustl.edu.ORCID http://orcid.org/0000-0002-0350-7574
Noelle V Frey *Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Boris Engels *Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
David M BarrettDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Olga ShestovaCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Pranali RavikumarCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Katherine D CumminsCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9041-0828
Yong Gu LeeCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Raymone PajarilloCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Inkook ChunCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Amy ShyuNovartis Institutes for Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6039-0408
Steven L HighfillNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Andrew PriceNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Linlin ZhaoNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Liaomin PengNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Brian GrandaNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Melissa RamonesNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Xueqing Maggie LuPenn Institute for Biomedical Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
David A ChristianDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jessica PerazzelliDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Simon F LaceyCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nathan H RoyDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Janis K BurkhardtDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8176-1375
Florent ColombThe Wistar Institute, Philadelphia, PA, USA.
Mohammad DamraThe Wistar Institute, Philadelphia, PA, USA.
Mohamed Abdel-MohsenThe Wistar Institute, Philadelphia, PA, USA.
Ting LiuDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
Dongfang LiuDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.ORCID http://orcid.org/0000-0002-7295-8088
Daron M StandleyResearch Institute for Microbial Diseases, Osaka, Japan.
Regina M YoungCenter for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Jennifer L BrogdonNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Stephan A GruppDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8030-7595
Carl H JuneDivision of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0241-3557
Shannon L Maude *Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Saar Gill *Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Marco Ruella *Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.ORCID http://orcid.org/0000-0003-4301-5811
University of Pennsylvania · USNovartis (United States) · USChildren's Hospital of Philadelphia · USThe Wistar Institute · USRutgers, The State University of New Jersey · USMicrobial Chemistry Research Foundation · JPParker Institute for Cancer Immunotherapy · USTranslational Therapeutics (United States) · USWashington University in St. Louis · US
Funding
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MProject 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Michael C. Milone · 2017 to 2026
$26.8MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MThe adaptor protein Crk in immune responsesR01AI130197 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Dongfang Liu · 2018 to 2026
$4.2MDefining and overcoming intrinsic T cell dysfunction to enable pediatric immunotherapyU01CA232361 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI GRUPP, STEPHAN A., WEBER, EVAN WILLIAM · 2019 to 2019
$3.7MDirecting the metabolic fate of CAR T cellsR01CA226983 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2018 to 2022
$2.1MCostimulatory ligand mobility effects on T cell activationR01GM104867 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI BURKHARDT, JANIS K. · 2013 to 2016
$1.3MThe adaptor protein Crk in immune responsesR56AI130197 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI LIU, DONGFANG · 2017 to 2023
$874kChimeric Antigen Receptor T cell Therapy for Acute Myeloid Leukemia (AML)K08CA194256 · NCI · UNIVERSITY OF PENNSYLVANIA · PI GILL, SAAR · 2015 to 2019
$839kResistance To Targeted Immunotherapies:CART19 as a ParadigmR00CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2018 to 2020
$608kBispecific cytotoxic lymphocytes in HIV-related lymphomaR21HL125018 · NHLBI · RBHS-NEW JERSEY MEDICAL SCHOOL · PI LIU, DONGFANG · 2015 to 2016
$449kHIV-1-Specific CTL Exhaustion at Immune SynapseR21AI124769 · NIAID · RBHS-NEW JERSEY MEDICAL SCHOOL · PI LIU, DONGFANG · 2016 to 2017
$446kNCI NIH HHS K08 CA194256NCI NIH HHS K99 CA212302NCI NIH HHS P01 CA214278NCI NIH HHS P30 CA010815NCI NIH HHS R00 CA212302NCI NIH HHS R01 CA226983NCI NIH HHS T32 CA009140NCI NIH HHS U01 CA232361NHLBI NIH HHS R21 HL125018NIAID NIH HHS R01 AI130197NIAID NIH HHS R21 AI124769NIAID NIH HHS R21 AI129594NIAID NIH HHS R56 AI130197NIGMS NIH HHS R01 GM104867
Abstract
While CD19-directed chimeric antigen receptor (CAR) T cells can induce remission in patients with B cell acute lymphoblastic leukemia (ALL), a large subset relapse with CD19
Indexed as
4-1BB LigandAdultAnimalsAntigens, CD19B-LymphocytesCD28 AntigensCells, CulturedChildChild, PreschoolFemaleHumansImmunotherapy, AdoptiveMaleMicePrecursor Cell Lymphoblastic Leukemia-LymphomaReceptors, Chimeric Antigen4-1BB LigandAntigens, CD19CD22 protein, humanCD28 AntigensReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2TNFRSF9 protein, humanTumor Necrosis Factor Receptor Superfamily, Member 9
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.