Retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for hepatocellular carcinoma

Abstract

The therapeutic effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system on hepatocellular carcinoma was studied in this experiment. The tk-containing retroviral recombinants were used to infect hepatoma cells (BEL-7402) and the cells were treated with ganciclovir (0-1000 μg/ ml). The results showed that HSV-tk gene could be efficiently transferred in vitro into hepatoma cells and stably expressed. The growth potential of the tk-containing cells was significantly inhibited by GCV (P < 0.01) as compared to the non-tkcontaining cells. The antitumor effect of HSV-tk/GCV system was also produced ex vivo in tk-containing tumor of nude mice as characterized by a marked decrease in tumor growth after GCV treatment contrary to a progressive enlargement of nontk-containing tumors. Although the histological examination demonstrated that the efficiency of the gene transfer was less than 30%, the killing effect of HSV-tk/GCV system on hepatocellular carcinoma was still significantly generated. The proper mechanism of HSV-tk gene therapy on hepatic tumor referred as bystander effect in therapeutic approach has not been found in this study and required to be explored further.

Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation

“…The above results indicated that the construction strategy of the recombinant vector was correctly performed and the retrovirus containing hHO-1 could be stably and efficiently expressed in transfected-VSMC. In fact, several other transgenic cell lines for expression of the specific target genes had been established in this lab by using retroviral [11], [20].…”

Suicide Gene Therapy by Herpes Simplex Virus-1 Thymidine Kinase (HSV-TK)

“…Ad.TK can be safely used in HCC patient upto 2X10 12 viral Particles/patient [35]. The HSV-TK gene has been successfully transferred into hepatoma cells (BEL-7402), and the growth potential of these cells was significantly inhibited by the application of GCV [36]. The bystander effect was further boosted by a combination therapy of co-expression of TK and E-cadherin genes in adenoviral vector.…”

Advances in Experimental and Translational Research in the Treatment of Hepatocellular Carcinoma

“…The difficulty of employing these modalities as a treatment for HCC is the ability to design a vector that would be specific for HCC and not the surrounding benign tissue [20]. Several viral vectors, including retroviral, lentiviral, adeno-associated viral (AAV), herpes viral, and adenoviral variations, are currently available for gene therapy and are being explored for HCC gene therapy [21][22][23]. In addition, Iwasaki et al have recently described the use of nanoparticles as a means of gene delivery.…”