Adenovirus-mediated interleukin-12 gene therapy for metastatic colon carcinoma

Manuel Caruso, Khiem Pham-Nguyen, Yok Lam Kwong, Bisong Xu, Ken Ichiro Kosai, Milton Finegold, Savio L C Woo, Shu Hsia Chen

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11302-11306
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - Oct 15 1996

Keywords

  • cytokines
  • gene transfer
  • recombinant adenoviral vectors

ASJC Scopus subject areas

  • General

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