IN-VIVO CANCER GENE-THERAPY WITH A RECOMBINANT INTERLEUKIN-2 ADENOVIRUS VECTOR

Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. In vivo therapy of established murine fibro sarcoma and mammary carcinomas was attempted with intratumoral injecti ons of a recombinant AdV vector in which the human interleukin-2 (IL-2 ) gene was driven by the cytomegalovirus enhancer/promoter. Delayed gr owth and rejection of some tumors could be achieved with a cumulative virus dose of 2 to 6 X 10(9) plaque-forming units in two or three divi ded doses. Lower viral doses were ineffective, and higher doses result ed in animal death due to IL-2 toxicity. Using AdV vectors with the ma rker genes beta-galactosidase and luciferase, it is clear that even sm all volume (10 to 20 mu L) intratumoral injections result in substanti al systemic delivery of a portion of the virus dose. These findings de fine the potential and limitations of in vivo AdV-based cancer gene th erapy and provide supper? for strategies to develop tumor-specific vec tors.