Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy.
To evaluate human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase (HSV-TK) -mediated gene therapy, we tested the utility of different viral vectors on three human cell lines DU-145, LNCaP, and PC-3. Our viral vectors were carrying a fusion gene of HSV-TK and green fluorescent protein for accurate determination of the gene transfer rate and its contribution to the treatment outcome in each case. We observed that adenoviral and lentiviral vectors were efficient vehicles for all the cell lines, whereas Semliki Forest virus and Sindbis virus vectors yielded only a few percent of transgene-positive cells. Despite sufficient gene transfer rates (25-45%) in the ganciclovir (GCV) sensitivity experiment, only DU-145 cells were efficiently destroyed under clinically relevant GCV concentrations. This was shown to be due to low level of "bystander effect" in PC-3 and LNCaP cells. Our data demonstrate that human prostate tumors can be good targets for adenovirus- or lentivirus-mediated HSV-TK/GCV gene therapy, but each tumor should be investigated for gene transfer rate and bystander effect to warrant a sufficient treatment result.
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
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S
Loimas
M R
MR
Toppinen
T
T
Visakorpi
J
J
Jänne
J
J
Wahlfors
D000256:Adenoviridae / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015774:Ganciclovir / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D012672:Semliki forest virus / Q000235:genetics; D012845:Sindbis Virus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic
D000998:Antiviral Agents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir