ADENOVIRUS-MEDIATED INTERLEUKIN-12 GENE-THERAPY FOR METASTATIC COLON-CARCINOMA

Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic impla ntation of a poorly immunogenic colon carcinoma cell line (MCA-26), wh ich is syngeneic in BALB/c mice. Intratumoral transfer of the herpes s implex virus type 1 thymidine kinase (HSV-tk) and the murine interleuk in (mIL)-2 genes resulted in substantial hepatic tumor regression, ind uced an effective systemic antitumoral immunity in the host and prolon ged the median survival time of the treated animals from 22 to 35 days . The antitumoral immunity declined gradually, which led to tumor recu rrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral adm inistration of this cytokine vector alone increased significantly surv ival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may a lso be an attractive treatment strategy for metastatic colon carcinoma .