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 implantation of
a poorly immunogenic colon carcinoma cell line (MCA-26),
which is syngeneic in BALB/c mice. Intratumoral transfer of
the herpes simplex virus type 1 thymidine kinase (HSV-tk)
and the murine interleukin (mIL)-2 genes resulted in substantial
hepatic tumor regression, induced an effective systemic
antitumoral immunity in the host and prolonged the
median survival time of the treated animals from 22 to 35
days. The antitumoral immunity declined gradually, which led
to tumor recurrence over time. A recombinant adenovirus
expressing the mIL-12 gene was constructed and tested in the
MCA-26 tumor model. Intratumoral administration of this
cytokine vector alone increased significantly survival 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
also be an attractive treatment strategy for metastatic colon
carcinoma.
Metastatic colon carcinoma is the second leading cause of