GENE-THERAPY OF RAT C6 GLIOMA USING ADENOVIRUS-MEDIATED TRANSFER OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE - LONG-TERM FOLLOW-UP BYMAGNETIC-RESONANCE-IMAGING

The herpes simplex virus thymidine kinase gene was transferred into C6 glioma cells by infection with a recombinant adenovirus. In vitro, a 10 muM ganciclovir concentration was able to kill 100% of the infected cells. For in vivo experiments, brain tumors were established by ster eotactic injection of C6 glioma cells in the caudate nucleus of rats. Five days later, the recombinant adenovirus was inoculated into the tu mors and the animals were treated by intraperitoneal injections of gan ciclovir for 14 days. At the end of ganciclovir therapy, histological examination revealed a 28-fold decrease in tumor volumes in the treate d animals, as compared with control animals. In long-term studies, the mean survival time of the treated animals was four-fold longer than t hat of control ones. Magnetic resonance imaging demonstrated an appare nt complete tumor regression in 62% of the animals. However, late tumo r recurrence was observed in the treated animals. Repeated inoculation of C6 glioma cells in the contralateral hemisphere of long-term survi ving animals resulted in either tumor rejection or slowly growing tumo rs. These findings demonstrate the potential efficacy of adenovirus-me diated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration in the treatment of rat gliomas.