Intra-arterial delivery of a recombinant adenovirus does not increase genetransfer to tumor cells in a rat model of metastatic colorectal carcinoma

Hepatic artery infusion of adenoviral vectors has been shown to increase tr ansduction of certain hepatocellular malignancies in preclinical studies. I n addition, clinical trials have begun evaluating the efficacy of gene tran sfer of cytotoxic genes to metastatic colorectal tumors through hepatic art ery infusion. Here we evaluate the extent of gene expression and therapeuti c effect following various routes of administration of recombinant adenovir us in a rat model of metastatic colorectal carcinoma. We administered adeno virus (AdCMVlacZ) to rats with established colorectal metastases through in fusion into the hepatic artery, intravenous infusion, or direct injection i nto a tumor. Intravenous administration resulted in transduction of hepatoc ytes, but not tumor cells. Hepatic arterial administration failed to substa ntially increase transduction of tumor cells. In addition, ligation of the hepatic artery following infusion of adenovirus or the addition of lipiodol infusion had no effect on the transduction of tumor cells. We administered AdCMVp53 by direct injection into tumors, intravenous administration, or h epatic artery infusion to evaluate the delivery of a therapeutic gene. Dire ct injection of AdCMVp53 into established hepatic colorectal metastases res ulted in a therapeutic response in comparison with both hepatic arterial an d intravenous infusion of vector. These preclinical studies fail to support a strategy of infusion through the hepatic artery of recombinant adenoviru s targeting tumor cells in the treatment of colorectal cancer liver metasta ses.