Combination gene therapy for liver metastasis of colon carcinoma in vivo

Shu Hsia Chen, X. H. Li Chen, Yibin Wang, Ken Ichiro Kosai, Milton J. Finegold, Susan S. Rich, Savio L.C. Woo

Research output: Contribution to journalArticlepeer-review

258 Scopus citations


The efficacy of combination therapy with a 'suicide gene' and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

Original languageEnglish
Pages (from-to)2577-2581
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - 28 Mar 1995
Externally publishedYes


  • cancer gene therapy
  • cancer vaccine
  • metastatic colon carcinoma
  • recombinant adenoviral vectors
  • suicide gene


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