Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy

• Published in: Cancer gene therapy Vol. 8; no. 2; pp. 137 - 144
• Main Authors: Loimas, S, Toppinen, M R, Visakorpi, T, Jänne, J, Wahlfors, J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2001
• Subjects: Adenoviridae - genetics; Antiviral Agents - therapeutic use; Expression vectors; Fusion protein; Ganciclovir; Ganciclovir - therapeutic use; Gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Green fluorescent protein; Green Fluorescent Proteins; Herpes simplex; Herpes simplex virus; Herpes viruses; Herpesvirus 1, Human - enzymology; Humans; Lentivirus - genetics; Luminescent Proteins - metabolism; Male; Prostate; Prostate cancer; Prostate carcinoma; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Prostatic Neoplasms - virology; Semliki forest virus - genetics; Sindbis Virus - genetics; Suicide; Suicide genes; Thymidine; Thymidine kinase; Thymidine Kinase - genetics; Transduction, Genetic; Tumors; Vectors (Biology); Viruses
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/sj.cgt.7700286

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.