The use of recombinant adeno-associated viral vectors for the transduction of epithelial tumor cells.
Using hight-titer recombinant adeno-associated viral vectors (rAAV), we have investigated the feasibility of cancer vaccines from tumor explants. In a first set of experiments, rAAV vectors expressing firefly luciferase reporter genes were used to transduce different human tumor cell lines. At day three post transduction, all of the human tumor cell lines tested showed high levels of luciferase expression. To further evaluate rAAV-mediated gene transfer efficiency into primary tumor cells, we transduced freshly isolated tumor cells from malignant melanoma and ovarian carcinoma patients. As a remarkable result, reporter gene expression in primary tumor cells was significantly higher than in the tested established tumor cell lines. These data could also be reproduced with a rAAV/lacZ vector, since the portion of successfully transduced primary tumor was higher than 90%. Taken together, our data demonstrate that rAAV-mediated gene transfer is a very efficient method for the transduction of freshly isolated human tumor cells and may allow the generation of potent autologous cancer vaccines.
Hoerer
M
M
MediGene AG, München Martinsried, Germany.
Bogedain
C
C
Scheer
U
U
Heberger
C
C
Steyrer
S
S
Burger
A
A
Maass
G
G
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D001517:Coleoptera / Q000201:enzymology / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D007763:Lac Operon; D008156:Luciferases / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015163:Superinfection; D014161:Transduction, Genetic / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D019384:Nucleic Acid Synthesis Inhibitors; D008156:Luciferases