Combination suicide and cytokine gene therapy for hepatic metastases of colon carcinoma: Sustained antitumor immunity prolongs animal survival

Shu Hsia Chen, Ken Ichiro Kosai, Bisong Xu, Khiem Pham-Nguyen, Charles Contant, Milton J. Finegold, Savio L C Woo

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

The effectiveness of combination therapy using a suicide gene and cytokine genes fur the treatment of metastatic colon carcinoma in the mouse liver was investigated. Pre-established hepatic tumors treated with a recombinant adenoviral vector containing the herpes simplex virus thymidine kinase gene (tk) exhibited substantial regression, although all treated animals suffered from subsequent relapses. Although cotreatment with a mouse interleukin 2 (mIL-2)-containing adenoviral vector induced an effective antitumor immune response, the immunity waned with time, and the treated animals eventually succumbed to hepatic tumor relapse or distant metastases. In this study, mouse granulocyte macrophage colony-stimulating factor (mGM- CSF) gene was tested for its ability to further enhance and prolong the antitumoral cellular immunity. A fraction of the animals treated with tk + mIL-2 + mGM-CSF developed long-term antitumor immunity and survived for more than 4 months without recurrence. This long-term antitumor immunity could be enhanced further by subsequent 'vaccination' with mIL-2-expressing parental tumor cells. The results indicate that local expression of GM-CSF in the hepatic tumors and prolonged mIL-2 expression are necessary to generate persistent antitumor immunity that is essential for the prevention of tumor recurrence and long-term animal survival.

Original languageEnglish (US)
Pages (from-to)3758-3762
Number of pages5
JournalCancer research
Volume56
Issue number16
StatePublished - Aug 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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