ArticleGene therapy2016
Optimized human CYP4B1 in combination with the alkylator prodrug 4-ipomeanol serves as a novel suicide gene system for adoptive T-cell therapies.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.BMC cancer · 2026Article
- Ionizing Radiation-Induced Structural Modification of Isoegomaketone and Its Anti-Inflammatory Activity.Molecules (Basel, Switzerland) · 2025Article
- Functional analysis of CYP4B1 enzymes from apes and humans uncovers evolutionary hot spots for adaptations of the catalytical function.PLoS genetics · 2025Article
- Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review.Cell death & disease · 2024Review
- Spotlight on CYP4B1.International journal of molecular sciences · 2023Review
- Optimized NGFR-derived hinges for rapid and efficient enrichment and detection of CAR T cellsMolecular therapy oncolytics · 2022Article
- Genetic Engineering and Enrichment of Human NK Cells for CAR-Enhanced Immunotherapy of Hematological Malignancies.Frontiers in immunology · 2022Article
- Advances in the Pharmacological Activities and Effects of Perilla Ketone and Isoegomaketone.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells.Molecular therapy oncolytics · 2021Article
- Review
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- Epigenetic Priming of Bladder Cancer Cells With Decitabine Increases Cytotoxicity of Human EGFR and CD44v6 CAR Engineered T-Cells.Frontiers in immunology · 2021Article
- Heterologous Expression and Functional Characterization of Novel CYP2C9 Variants Identified in the Alaska Native People.The Journal of pharmacology and experimental therapeutics · 2020Article
- Novel insights into oxidation of fatty acids and fatty alcohols by cytochrome P450 monooxygenase CYP4B1.Archives of biochemistry and biophysics · 2020Article
- Deficiency of the Fanconi anemia E2 ubiqitin conjugase UBE2T only partially abrogates Alu-mediated recombination in a new model of homology dependent recombination.Nucleic acids research · 2019Article
- Influence of Stereochemistry on the Bioactivation and Glucuronidation of 4-Ipomeanol.The Journal of pharmacology and experimental therapeutics · 2019Article
- Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models.Oncogene · 2018Article
- Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.Frontiers in oncology · 2018Review
- Development of novel target modules for retargeting of UniCAR T cells to GD2 positive tumor cells.Oncotarget · 2017Article
- Ligand characterization of CYP4B1 isoforms modified for high-level expression in Escherichia coli and HepG2 cells.Protein engineering, design & selection : PEDS · 2017Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
Engineering autologous or allogeneic T cells to express a suicide gene can control potential toxicity in adoptive T-cell therapies. We recently reported the development of a novel human suicide gene system that is based on an orphan human cytochrome P450 enzyme, CYP4B1, and the naturally occurring alkylator prodrug 4-ipomeanol. The goal of this study was to systematically develop a clinically applicable self-inactivating lentiviral vector for efficient co-expression of CYP4B1 as an ER-located protein with two distinct types of cell surface proteins, either MACS selection genes for donor lymphocyte infusions after allogeneic stem cell transplantation or chimeric antigen receptors for retargeting primary T cells. The U3 region of the myeloproliferative sarcoma virus in combination with the T2A site was found to drive high-level expression of our CYP4B1 mutant with truncated CD34 or CD271 as MACS suitable selection markers. This lentiviral vector backbone was also well suited for co-expression of CYP4B1 with a codon-optimized CD19 chimeric antigen receptor (CAR) construct. Finally, 4-ipomeanol efficiently induced apoptosis in primary T cells that co-express mutant CYP4B1 and the divergently located MACS selection and CAR genes. In conclusion, we here developed a clinically suited lentiviral vector that supports high-level co-expression of cell surface proteins with a potent novel human suicide gene.
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