[Gene therapy using recombinant adenovirus carrying herpes simplex-thymidine kinase gene to treat mouse B 16 melanoma in vivo].

Adenoviral transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by administration of gancyclovir (GCV) was used to treat B 16 melanoma of C 57 BL/6 mice. B 16 murine melanoma cells transduced in vitro by a recombinant replication-defective adenovirus containing the HSV-tk gene [Ad(HSV-tk)] were highly sensitive to cell killing by GCV, and the IC50 was 0.1 microgram/ml. A significant "bystander effect" was observed when Ad(HSV-tk)-infected and -uninfected B 16 cells were mixed. Direct tumoral injection of Ad (HSV-tk) into established B 16 melanoma in C 57 BL/6 mice and subsequent treatment for 6 d with GCV resulted in the growth regression and necrosis of tumor nodules, and the tumor size was approximately reduced to one-twenty fifth of that of control animals. Finally, the safety of this treatment approach was demonstrated by limited dissemination of virus using sensitive RT-PCR. HSV-tk mRNA was detected only in the tumor nodule. These data indicated that gene therapy using Ad(HSV-tk)/GCV may function as an effective and safe alternative for treatment of melanoma in vivo.