Rosuvastatin Enhances VSV-G Lentiviral Transduction of NK Cells via Upregulation of the Low-Density Lipoprotein Receptor
| Autor: | Ying Gong, Gerard M. J. Bos, Ian Janssen, Roel G. J. Klein Wolterink, Arjan J. Groot, Wilfred T. V. Germeraad |
|---|---|
| Přispěvatelé: | Interne Geneeskunde, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Hematologie (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:QH426-470 Cytotoxicity Natural-killer-cells Efficient gene-transfer LDL RECEPTOR Article statins Cell therapy 03 medical and health sciences Transduction (genetics) 0302 clinical medicine Downregulation and upregulation INFECTION Genetics Cytotoxic T cell GGPP lcsh:QH573-671 VSV-G Receptor Molecular Biology natural killer cells biology Chemistry lcsh:Cytology T-cells LIPOPHILIC STATINS Vector transduction lentiviral transduction nutritional and metabolic diseases biology.organism_classification CHIMERIC ANTIGEN RECEPTOR 3. Good health lcsh:Genetics 030104 developmental biology LDLR HEMATOPOIETIC STEM Vesicular stomatitis virus 030220 oncology & carcinogenesis LDL receptor Cancer research Molecular Medicine lipids (amino acids peptides and proteins) rosuvastatin |
| Zdroj: | Molecular Therapy. Methods & Clinical Development Molecular Therapy-Methods and Clinical Development, 17, 634-646. Nature Publishing Group Molecular Therapy: Methods & Clinical Development, Vol 17, Iss, Pp 634-646 (2020) |
| ISSN: | 2329-0501 |
| Popis: | Adoptive natural killer (NK) cell therapy is attaining promising clinical outcomes in recent years, but improvements are needed. Genetic modification of NK cells with a tumor antigen-specific receptor on their surface coupled to intracellular signaling domains may lead to enhanced cytotoxicity against malignant cells. One of the most common approaches is by lentivirus-mediated transduction. However, NK cells are difficult to transduce and various methods have been attempted with different success rates. Because the low-density lipoprotein-receptor (LDLR) is the receptor of vesicular stomatitis virus (VSV) and is expressed only at low levels on NK cells, we tested the potential of 5 statins and 5 non-statin compounds to increase the LDLR expression, thereby facilitating viral transduction. We found that the transduction efficiency of VSV-G pseudotyped lentivirus is augmented by statins that induced higher LDLR expression. In both NK-92 cells and primary NK cells, the transduction efficiency increased after treatment with statins. Furthermore, statins have been reported to suppress NK cell cytotoxicity; however, we showed that this can be completely reversed by adding geranylgeranyl-pyrophosphate (GGPP). Among the statins tested, we found that the combination of rosuvastatin with GGPP most potently improved viral transduction without affecting the cytotoxic properties of the NK cells. Graphical Abstract Natural killer (NK) cells are known to be difficult to transduce, and various methods have been attempted with different success rates. Gong and colleagues found that the combination of rosuvastatin with GGPP most potently improved VSV-G lentivirus transduction via upregulating cell surface LDLR without affecting the cytotoxic properties of the NK cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|