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In vitro exploration of a myeloid-derived suppressor cell line as vehicle for cancer gene therapy

(2017) CANCER GENE THERAPY. 24(4). p.149-155
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Abstract
Recent research indicates that cell-mediated gene therapy can be an interesting method to obtain intratumoral expression of therapeutic proteins. This paper explores the possibility of using transfected myeloid-derived suppressor cells (MDSCs), derived from a murine cell line, as cellular vehicles for transporting plasmid DNA (pDNA) encoding interleukin-12 (IL-12) to tumors. Transfecting these cells via electroporation caused massive cell death. This was not due to electroporation-induced cell damage, but was mainly the result of the intracellular presence of plasmids. In contrast, pDNA transfection using Lipofectamine 2000 (LF2000) did not result in a significant loss of viability. Differences in delivery mechanism may explain the distinctive effects on cell viability. Indeed, electroporation is expected to cause a rapid and massive influx of pDNA resulting in cytosolic pDNA levels that most likely surpass the activation threshold of the intracellular DNA sensors leading to cell death. In contrast, a more sustained intracellular release of the pDNA is expected with LF2000. After lipofection with LF2000, 56% of the MDSCs were transfected and transgene expression lasted for at least 24 h. Moreover, biologically relevant amounts of IL-12 were produced by the MDSCs after lipofection with an IL-12 encoding pDNA. In addition, IL-12 transfection caused a significant upregulation of CD80 and considerably reduced the immunosuppressive capacity of the MDSCs. IL-12-transfected MDSCs were still able to migrate to tumor cells, albeit that lipofection of the MDSCs seemed to slightly decrease their migration capacity.
Keywords
MESENCHYMAL STEM-CELLS, T-CELLS, INTERLEUKIN-12, TUMOR, DNA, MICE, IMMUNOTHERAPY, DELIVERY, IL-12, ELECTROTRANSFER

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MLA
Denies, Sofie et al. “In Vitro Exploration of a Myeloid-derived Suppressor Cell Line as Vehicle for Cancer Gene Therapy.” CANCER GENE THERAPY 24.4 (2017): 149–155. Print.
APA
Denies, S., Combes, F., Ghekiere, C., Mc Cafferty, S., Cicchelero E, L., & Sanders, N. (2017). In vitro exploration of a myeloid-derived suppressor cell line as vehicle for cancer gene therapy. CANCER GENE THERAPY, 24(4), 149–155.
Chicago author-date
Denies, Sofie, Francis Combes, Cynthia Ghekiere, Séan Mc Cafferty, Laetitia Cicchelero E, and Niek Sanders. 2017. “In Vitro Exploration of a Myeloid-derived Suppressor Cell Line as Vehicle for Cancer Gene Therapy.” Cancer Gene Therapy 24 (4): 149–155.
Chicago author-date (all authors)
Denies, Sofie, Francis Combes, Cynthia Ghekiere, Séan Mc Cafferty, Laetitia Cicchelero E, and Niek Sanders. 2017. “In Vitro Exploration of a Myeloid-derived Suppressor Cell Line as Vehicle for Cancer Gene Therapy.” Cancer Gene Therapy 24 (4): 149–155.
Vancouver
1.
Denies S, Combes F, Ghekiere C, Mc Cafferty S, Cicchelero E L, Sanders N. In vitro exploration of a myeloid-derived suppressor cell line as vehicle for cancer gene therapy. CANCER GENE THERAPY. 2017;24(4):149–55.
IEEE
[1]
S. Denies, F. Combes, C. Ghekiere, S. Mc Cafferty, L. Cicchelero E, and N. Sanders, “In vitro exploration of a myeloid-derived suppressor cell line as vehicle for cancer gene therapy,” CANCER GENE THERAPY, vol. 24, no. 4, pp. 149–155, 2017.
@article{8525370,
  abstract     = {Recent research indicates that cell-mediated gene therapy can be an interesting method to obtain intratumoral expression of therapeutic proteins. This paper explores the possibility of using transfected myeloid-derived suppressor cells (MDSCs), derived from a murine cell line, as cellular vehicles for transporting plasmid DNA (pDNA) encoding interleukin-12 (IL-12) to tumors. Transfecting these cells via electroporation caused massive cell death. This was not due to electroporation-induced cell damage, but was mainly the result of the intracellular presence of plasmids. In contrast, pDNA transfection using Lipofectamine 2000 (LF2000) did not result in a significant loss of viability. Differences in delivery mechanism may explain the distinctive effects on cell viability. Indeed, electroporation is expected to cause a rapid and massive influx of pDNA resulting in cytosolic pDNA levels that most likely surpass the activation threshold of the intracellular DNA sensors leading to cell death. In contrast, a more sustained intracellular release of the pDNA is expected with LF2000. After lipofection with LF2000, 56% of the MDSCs were transfected and transgene expression lasted for at least 24 h. Moreover, biologically relevant amounts of IL-12 were produced by the MDSCs after lipofection with an IL-12 encoding pDNA. In addition, IL-12 transfection caused a significant upregulation of CD80 and considerably reduced the immunosuppressive capacity of the MDSCs. IL-12-transfected MDSCs were still able to migrate to tumor cells, albeit that lipofection of the MDSCs seemed to slightly decrease their migration capacity.},
  author       = {Denies, Sofie and Combes, Francis and Ghekiere, Cynthia and Mc Cafferty, Séan and Cicchelero, Laetitia and Sanders, Niek},
  issn         = {0929-1903},
  journal      = {CANCER GENE THERAPY},
  keywords     = {MESENCHYMAL STEM-CELLS,T-CELLS,INTERLEUKIN-12,TUMOR,DNA,MICE,IMMUNOTHERAPY,DELIVERY,IL-12,ELECTROTRANSFER},
  language     = {eng},
  number       = {4},
  pages        = {149--155},
  title        = {In vitro exploration of a myeloid-derived suppressor cell line as vehicle for cancer gene therapy},
  url          = {http://dx.doi.org/10.1038/cgt.2016.60},
  volume       = {24},
  year         = {2017},
}

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