ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
CAR Gene Delivery by T-cell Targeted Lentiviral Vectors is Enhanced by Rapamycin Induced Reduction of Antiviral Mechanisms.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 12 citations in OpenAlex.
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.Molecular biomedicine · 2026Review
- Targeting the pMHC-TCR Interaction: Molecular Strategies and Therapeutic Potential in Autoimmunity.International journal of molecular sciences · 2026Review
- Optimizing In Vivo CAR T-cell Engineering for Cancer Immunotherapy.Cancer research · 2026Review
- Review
- Review
- Delivery platforms forFrontiers in immunology · 2026Review
- A novel gene delivery platform based on a commensal human anellovirus demonstrates transduction in multiple tissue types.Molecular therapy. Methods & clinical development · 2025Article
- State of the art in CAR-based therapy: In vivo CAR production as a revolution in cell-based cancer treatment.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- An overview on in-vivo generation of CAR-T cells using CRISPR-loaded functionalized nanocarriers for treating B-cell lineage acute lymphoblastic leukemia.Molecular biology reports · 2025Review
- Optimizing viral transduction in immune cell therapy manufacturing: key process design considerations.Journal of translational medicine · 2025Review
- From Multi-Omics to Visualization and Beyond: Bridging Micro and Macro Insights in CAR-T Cell Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Chimeric antigen receptor T-cell therapy in autoimmune diseases.Frontiers in immunology · 2024Review
- CAR Gene Delivery by T-cell Targeted Lentiviral Vectors is Enhanced by Rapamycin Induced Reduction of Antiviral Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Lentiviral vectors (LV) have become the dominant tool for stable gene transfer into lymphocytes including chimeric antigen receptor (CAR) gene delivery to T cells, a major breakthrough in cancer therapy. Yet, room for improvement remains, especially for the latest LV generations delivering genes selectively into T cell subtypes, a key requirement for in vivo CAR T cell generation. Toward improving gene transfer rates with these vectors, whole transcriptome analyses on human T lymphocytes are conducted after exposure to CAR-encoding conventional vectors (VSV-LV) and vectors targeted to CD8+ (CD8-LV) or CD4+ T cells (CD4-LV). Genes related to quiescence and antiviral restriction are found to be upregulated in CAR-negative cells exposed to all types of LVs. Down-modulation of various antiviral restriction factors, including the interferon-induced transmembrane proteins (IFITMs) is achieved with rapamycin as verified by mass spectrometry (LC-MS). Strikingly, rapamycin enhances transduction by up to 7-fold for CD8-LV and CD4-LV without compromising CAR T cell activities but does not improve VSV-LV. When administered to humanized mice, CD8-LV results in higher rates of green fluorescent protein (GFP) gene delivery. Also in vivo CAR T cell generation is improved in kinetics and tumor control, however to a moderate extent, leaving room for improvement by optimizing the rapamycin administration schedule. The data favor multi-omics approaches for improvements in gene delivery.
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Registered trials
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.