M. Caruso et al., ADENOVIRUS-MEDIATED INTERLEUKIN-12 GENE-THERAPY FOR METASTATIC COLON-CARCINOMA, Proceedings of the National Academy of Sciences of the United Statesof America, 93(21), 1996, pp. 11302-11306
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
.