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 implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (21), p.11302-11306
Main Authors: Caruso, Manuel, Pham-Nguyen, Khiem, Kwong, Yok-Lam, Xu, Bisong, Kosai, Ken-Ichiro, Finegold, Milton, Savio L. C. Woo, Chen, Shu-Hsia
Format: Article
Language:English
Subjects:
Adenoviridae
adenovirus
Animals
Cancer
Carcinoma
Cell Line
Cell lines
Cellular biology
Colon cancer
Colonic Neoplasms - immunology
Colonic Neoplasms - pathology
Colonic Neoplasms - therapy
Cytokines
Gene therapy
Genetic Therapy
Genetic Vectors
herpes simplex virus 1
Interleukin-12 - genetics
Interleukin-12 - therapeutic use
Liver
Liver Neoplasms - immunology
Liver Neoplasms - pathology
Liver Neoplasms - secondary
Liver Neoplasms - therapy
Mice
Mice, Inbred BALB C
Natural killer cells
Papers from a Colloquium
Recombinant Proteins - biosynthesis
T lymphocytes
T-Lymphocytes, Cytotoxic - immunology
Thymidine Kinase - biosynthesis
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.21.11302