ArticleJournal of translational medicine2022
Genome-wide profiling of retroviral DNA integration and its effect on clinical pre-infusion CAR T-cell products.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The trial behind it
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Who cites it
41 citing papers in PubMed, 48 citations in OpenAlex.
- Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study.The Lancet. Neurology · 2023Trial
- Transduction efficiency in clinical CAR T cell products: A retrospective study at a single center.Molecular therapy. Advances · 2026Article
- A review of genetic modification for ex vivo cellular therapies.Transfusion · 2026Article
- Genome-Wide Integration Site Profiling of Multi-Component CAR T-Cell Engineering Systems with ADA1/CD26 Co-Transduction.Biomedicines · 2026Article
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- LVV SMRTcap reveals extensive proviral variation in lentiviral vector-transduced CAR T cells.bioRxiv : the preprint server for biology · 2026Article
- CAR-mediated release of IL-10 increases the function of regulatory T cells: Relevance for future clinical application.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Chemistry-mediated synthetic virus-cell interaction as a generic approach to enhance gene delivery to mammalian cells.Molecular therapy. Advances · 2026Article
- A universal platform for simultaneous TCRα/β removal enables safer and more potent TCR therapies and autoimmune modeling.bioRxiv : the preprint server for biology · 2026Article
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
- Secondary Malignancies of Chimeric Antigen Receptor T-cell Therapy: A Multidimensional Analysis of Mechanisms, Risk Factors, and Treatment Strategies.Anti-cancer agents in medicinal chemistry · 2026Review
- Review
- In vivo CAR-T cell therapy: New breakthroughs for cell-based tumor immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Activity-based selection for enhanced base editor mutational scanning.Nature genetics · 2025Article
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- Review
- Interlaboratory assessment of candidate reference materials for lentiviral vector copy number and integration site measurements.Molecular therapy. Methods & clinical development · 2025Article
- Closing the gap: Nonviral TFAMoplex transfection boosted by bZIP domains compared to AAV-mediated transduction.Molecular therapy. Nucleic acids · 2025Article
- Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.Journal for immunotherapy of cancer · 2025Review
- Methodological landscape in the field of integration site identification of retroviruses and retroviral vectors.Frontiers in bioengineering and biotechnology · 2025Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundClinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are the most commonly used vectors in the manufacturing process. However, the integration pattern of these viral vectors and subsequent effect on CAR T-cell products is still unclear.
methodsWe used a modified viral integration sites analysis (VISA) pipeline to evaluate viral integration events around the whole genome in pre-infusion CAR T-cell products. We compared the differences of integration pattern between lentiviral and γ-retroviral products. We also explored whether the integration sites correlated with clinical outcomes.
resultsWe found that γ-retroviral vectors were more likely to insert than lentiviral vectors into promoter, untranslated, and exon regions, while lentiviral vector integration sites were more likely to occur in intron and intergenic regions. Some integration events affected gene expression at the transcriptional and post-transcriptional level. Moreover, γ-retroviral vectors showed a stronger impact on the host transcriptome. Analysis of individuals with different clinical outcomes revealed genes with differential enrichment of integration events. These genes may affect biological functions by interrupting amino acid sequences and generating abnormal proteins, instead of by affecting mRNA expression. These results suggest that vector integration is associated with CAR T-cell efficacy and clinical responses.
conclusionWe found differences in integration patterns, insertion hotspots and effects on gene expression vary between lentiviral and γ-retroviral vectors used in CAR T-cell products and established a foundation upon which we can conduct further analyses.
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