Gene delivery in malignant B cells using the combination of lentiviruses conjugated to anti-transferrin receptor antibodies and an immunoglobulin promoter
| Autor: | Leoh, Lai Sum, Morizono, Kouki, Kershaw, Kathleen M, Chen, Irvin SY, Penichet, Manuel L, Daniels-Wells, Tracy R |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
T-Lymphocytes
Recombinant Fusion Proteins Green Fluorescent Proteins Genetic Vectors Clinical Sciences Flucytosine malignant B cells Antibodies Vesicular stomatitis Indiana virus Cell Line Cytosine Deaminase Promoter Regions Jurkat Cells Transduction Genetic lentivirus Neoplasms antibody Receptors Humans Prodrugs Pentosyltransferases Antigens B-Lymphocytes prodrug therapy Tumor Transferrin Genetic Therapy transferrin receptor gene therapy CD HEK293 Cells Biotechnology |
| Zdroj: | Leoh, LS; Morizono, K; Kershaw, KM; Chen, ISY; Penichet, ML; & Daniels-Wells, TR. (2014). Gene delivery in malignant B cells using the combination of lentiviruses conjugated to anti-transferrin receptor antibodies and an immunoglobulin promoter. Journal of Gene Medicine, 16(1-2), 11-27. doi: 10.1002/jgm.2754. UCLA: Retrieved from: http://www.escholarship.org/uc/item/8nk5w9c4 The journal of gene medicine, vol 16, iss 1-2 |
| DOI: | 10.1002/jgm.2754. |
| Popis: | Background: We previously developed an antibody-avidin fusion protein (ch128.1Av) specific for the human transferrin receptor 1 (TfR1; CD71) to be used as a delivery vector for cancer therapy and showed that ch128.1Av delivers the biotinylated plant toxin saporin-6 into malignant B cells. However, as a result of widespread expression of TfR1, delivery of the toxin to normal cells is a concern. Therefore, we explored the potential of a dual targeted lentiviral-mediated gene therapy strategy to restrict gene expression to malignant B cells. Targeting occurs through the use of ch128.1Av or its parental antibody without avidin (ch128.1) and through transcriptional regulation using an immunoglobulin promoter. Methods: Flow cytometry was used to detect the expression of enhanced green fluorescent protein (EGFP) in a panel of cell lines. Cell viability after specific delivery of the therapeutic gene FCU1, a chimeric enzyme consisting of cytosine deaminase genetically fused to uracil phosphoribosyltransferse that converts the 5-fluorocytosine (5-FC) prodrug into toxic metabolites, was monitored using the MTS or WST-1 viability assay. Results: We found that EGFP was specifically expressed in a panel of human malignant B-cell lines, but not in human malignant T-cell lines. EGFP expression was observed in all cell lines when a ubiquitous promoter was used. Furthermore, we show the decrease of cell viability in malignant plasma cells in the presence of 5-FC and the FCU1 gene. Conclusions: The present study demonstrates that gene expression can be restricted to malignant B cells and suggests that this dual targeted gene therapy strategy may help to circumvent the potential side effects of certain TfR1-targeted protein delivery approaches. © 2014 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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