Selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins.
Malignant gliomas are the most frequent primary brain tumors and have a dismal prognosis due to their infiltrative growth. Gene therapy using viral vectors represents an attractive alternative to conventional cancer therapies. In a previous study, we established lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus (LCMV) glycoproteins (GPs) and demonstrated transduction of human malignant glioma cells in culture. In the current approach, we compared the transduction efficacy of LCMV-GP- and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral vectors for malignant glioma cells and normal brain cells in vitro and in vivo. LCMV-GP pseudotypes transduced almost exclusively astrocytes, whereas VSV-G pseudotypes infected neurons as well as astrocytes. LCMV-GP pseudotypes showed an efficient transduction of solid glioma parts and specific transduction of infiltrating tumor cells. In contrast, VSV-G-pseudotyped lentiviral vectors transduced only a few tumor cells in solid tumor parts and infected mostly normal brain cells in infiltrating tumor areas. In conclusion, lentiviral vectors pseudotyped with LCMV glycoproteins represent an attractive option for gene therapy of malignant glioma.
Miletic
Hrvoje
H
Abteilung für Neuropathologie, Universität zu Köln, D-50931 Cologne, Germany. h.miletic@uni-koeln.de
Fischer
Yvonne Heidemarie
YH
Neumann
Harald
H
Hans
Volkmar
V
Stenzel
Werner
W
Giroglou
Tsanan
T
Hermann
Manuel
M
Deckert
Martina
M
Von Laer
Dorothee
D
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D006023:Glycoproteins / Q000235:genetics*; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008164:Luminescent Proteins / Q000494:pharmacology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar
D006023:Glycoproteins; D008164:Luminescent Proteins; C413663:fluorescent protein 583