INTRATUMORAL INJECTION OF A CONCENTRATED ANTISENSE CYCLIN G1 RETROVIRAL VECTOR INHIBITS GROWTH OF UNDIFFERENTIATED CARCINOMA IN NUDE-MICE

Metastatic carcinoma is a potential target for experimental gene thera pies because it is refractory to conventional treatment and is invaria bly associated with poor survival. In this study, we tested the effica cy of intratumoral injection of a concentrated retroviral vector beari ng an antisense cyclin G1 construct in inhibiting the growth of VX2 ca rcinoma tumors implanted subcutaneously in nude mice. One hundred micr oliters of the retroviral vector supenatant (infectious titer, 1 x 10( 8) colony-forming units/ml) was injected directly into rapidly growing tumors every day, for a period of 2 weeks. Tumor growth was markedly inhibited in the mice that received the antisense cyclin G1 vector, wh en compared with tumor growth in mice receiving the control vector (p < 0.05 at 7 days, p < 0.001 at 11 days, and p < 0.05 at 21 days). Thes e findings represent the first demonstration of in vivo antitumor acti vity of an antisense cyclin G1 retroviral vector against undifferentia ted carcinoma and affirm the potential utility of antisense cyclin G1 retroviral vectors in the development of novel gene therapy approaches to metastatic carcinoma.