Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells
| Autor: | Anja Ehrhardt, Jian Gao, Fengmin Lu, Wenli Zhang, Kemal Mese, Oskar Bunz |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncolytic adenovirus lcsh:QH426-470 lcsh:Cytology viruses Genetic enhancement biochemical phenomena metabolism and nutrition Biology Article Viral vector Cell biology Oncolytic virus lcsh:Genetics 03 medical and health sciences Transduction (genetics) 030104 developmental biology 0302 clinical medicine NK-92 Cell culture 030220 oncology & carcinogenesis Genetics Molecular Medicine Telomerase reverse transcriptase lcsh:QH573-671 Molecular Biology |
| Zdroj: | Molecular Therapy. Methods & Clinical Development Molecular Therapy: Methods & Clinical Development, Vol 18, Iss, Pp 376-389 (2020) |
| ISSN: | 2329-0501 |
| DOI: | 10.1016/j.omtm.2020.06.010 |
| Popis: | Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology for an Ad type 5 (Ad5) vector temporally carrying a knob from Ad37. We constructed a producer cell line stably expressing a fused Ad5/37 chimeric fiber comprising the Ad5 shaft-tail and the Ad37 knob and a miRNA inhibiting Ad5 knob expression (HEK293-Ad5/37-miRNA). The chimeric Ad5/37 vector resulted in enhanced transduction rates in Ad37 adequately and Ad5 poorly transduced cells. Particularly, encapsidation of the oncolytic Ad5-human telomerase reverse transcriptase (hTERT) vector genome into the chimeric Ad5/37 capsid showed efficient transduction of NK-92 carrier cells. These infected carrier cells then delivered the oncolytic vector to tumor cells, which resulted in enhanced Ad5-hTERT-mediated tumor cell killing. We show that this transiently capsid-modified chimeric vector carrying an Ad5 genome displayed higher transduction efficiencies of natural killer cell-derived NK-92 cells utilized as carriers in cancer immune therapy. In summary, transiently modified adenoviral vectors will have important implications for cancer and gene therapy. Graphical Abstract We constructed a producer cell line expressing a fused Ad5/37 chimeric fiber comprising the Ad5 shaft-tail and the Ad37 knob. The chimeric Ad5/37 vector results in enhanced transduction of oncolytic Ad5-hTERT into NK-92 carrier cells, which can then be used to deliver oncolytic Ad5-hTERT to tumor cells, leading to enhanced Ad5-hTERT-mediated tumor cell killing. |
| Databáze: | OpenAIRE |
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