ArticleNature medicine2025
Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.
Abstract read
In one paragraph
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
–field-weighted citation impact
What it found
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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
53 citing papers in PubMed.
- Decade-long persistence of CD19 CAR T cells in B cell lymphomas.Nature medicine · 2026Trial
- Advancing In Vivo Chimeric Antigen Receptor T-Cell Engineering to Accelerate Clinical Translation.MedComm · 2026Review
- CAR-T therapy for immune-mediated necrotizing myopathy: a review of mechanisms and emerging clinical evidence.Clinical rheumatology · 2026Review
- A review of genetic modification for ex vivo cellular therapies.Transfusion · 2026Article
- CAR-T cell therapy: potential for paediatric brain tumours-an update.Journal of neuro-oncology · 2026Review
- T cell receptor repertoire dynamics and newly identified functional regulators of autologous tumor-infiltrating lymphocyte therapy in advanced solid tumors.Journal of translational medicine · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen-Directed CAR T-Cell Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- High-titer modular retroviral vectors enabled by an antisense cassette design preventing dsRNA formation during virus production.Molecular therapy. Advances · 2026Article
- Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation.Cell stem cell · 2026Article
- LVV SMRTcap reveals extensive proviral variation in lentiviral vector-transduced CAR T cells.bioRxiv : the preprint server for biology · 2026Article
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Systematic Review of Immunosuppression After Chimeric Antigen Receptor T-Cell Therapy for Posttransplant Lymphoproliferative Disorder.Kidney international reports · 2026Article
- Data-informed optimization of CAR T-cell therapy long-term follow-up.Journal for immunotherapy of cancer · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- IL-18-Mediated Tumor Immune Evasion.Current issues in molecular biology · 2026Review
- PRISM-Seq: An Ultra-sensitive Sequencing Approach For Mapping Lentiviral Integration Sites.bioRxiv : the preprint server for biology · 2026Article
- CD4Nature medicine · 2026Article
- Protein-only centromeric chromatin assembly streamlines human artificial chromosome formation.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
66 authors.
Julie K Jadlowsky *Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0005-5115-1321
Elizabeth O Hexner *Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1125-4060
Amy MarshallCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stephan A GruppDepartment of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8030-7595
Noelle V FreyDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
James L RileyCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1057-576X
Elizabeth VelosoCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Holly McConvilleCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Walter RogalCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cory CzuczmanCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0005-1127-8651
Wei-Ting HwangAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2829-2167
Yimei LiDepartment of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9067-6992
Rachel M LeskowitzCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0583-8446
Olivia FarrellyCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jayashree KararCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shannon ChristensenCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Julie Barber-RotenbergCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Avery GaymonCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Naomi AronsonDepartment of Medicine, Division of Infectious Diseases, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Wendy BernsteinDepartment of Medicine, Division of Infectious Diseases, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Jan Joseph MelenhorstCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7677-537X
Aoife M RocheDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John K EverettDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sonja A ZolnoskiDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alexander G McFarlandDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shantan ReddyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Angelina PetrichenkoDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0600-0709
Emma J CookDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0006-9073-6194
Carole LeeDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0002-3724-6373
Vanessa E GonzalezCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kathleen AlexanderCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Irina KulikovskayaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ángel Ramírez-FernándezCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Janna C MinehartDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8053-690X
Marco RuellaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4301-5811
Saar I GillCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stephen J SchusterDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3376-8978
Adam D CohenDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0939-3843
Alfred L GarfallDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2791-5748
Payal D ShahDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
David L PorterDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shannon L MaudeCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bruce L LevineCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6971-8465
Donald L SiegelCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2098-2251
Anne ChewCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stephen McKennaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lester LledoCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Megan M DavisCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Gabriela PlesaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4279-5943
Friederike HerbstCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2167-750X
Edward A StadtmauerDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Pablo TebasDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Amanda DiNofiaDepartment of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Andrew HaasDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Naomi B HaasDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8907-7968
Regina MyersDepartment of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Donald M O'RourkeCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8479-7314
Jakub SvobodaDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Janos L TanyiAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Richard AplencDepartment of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jeffrey M JacobsonDepartment of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Andrew H KoDepartment of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA, USA.
Roger B CohenDepartment of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Carl H JuneCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.ORCID http://orcid.org/0000-0003-0241-3557
Frederic D BushmanDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. bushman@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-4740-4056
Joseph A FraiettaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jfrai@upenn.edu.ORCID http://orcid.org/0000-0001-7900-8993
Funding
Project 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Joseph Anthony Fraietta · 2017 to 2026
$26.8MLinking insertional mutagenesis and cell function to improve CAR T cell therapyR01CA241762 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D, MELENHORST, JAN J · 2019 to 2023
$3.1MNCI NIH HHS P01 CA214278U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER) P01CA214278U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER) R01CA241762
Abstract
Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer. Eighteen patients (2.3%) developed secondary malignancies after treatment, with a median onset of 1.94 years (range: 51 d to 14 years). Where possible, incident tumor samples were analyzed for vector copy number, revealing no evidence of high-level marking or other indications of insertional mutagenesis. One T cell lymphoma was detected, but malignant T cells were not marked by vector integration. Analysis of vector integration sites in 176 patients revealed no pathological insertions linked to secondary malignancies, although, in some cases, integration in or near specific genes, including tumor suppressor genes, was associated with modest clonal expansion and sustained T cell persistence. These findings highlight the safety of engineered T cell therapies.
Indexed as
GammaretrovirusGenetic TherapyLentivirusT-LymphocytesAdultFemaleGenetic VectorsHIV InfectionsHumansMaleMiddle AgedNeoplasms
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PMID
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