Selective killing of osteosarcoma cells in culture after retroviral mediated gene transfer of a herpes simplex thymidine kinase suicide gene.
As conventional therapy of osteosarcoma is aggressive and its success relatively poor, notably in cases relapse, we investigated the therapeutic effect of retroviral herpes simplex thymidine kinase (HSV1-TK) gene transfer into a human osteosarcoma cell line. Transfected target cells are sensitive to ganciclovir (GCV) (IC50 0.1 microM), and a potent bystander effect, by which cell death can be induced in HSV1-TK negative dividing cells located in the vicinity of HSV1-TK positive ones, is demonstrated. This is significant for clinical applications as no available gene transfer method can achieve 100% transduction to target cells.
Grossin
L
L
Laboratoire de Biochimie et de Biologie Moléculaire, Faculté de Médecine, Limoges, France.
Charissoux
J L
JL
Teissier
M P
MP
Rigaud
M
M
D015774:Ganciclovir / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D012190:Retroviridae / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D013937:Thymidine Kinase; D015774:Ganciclovir