Tumor dormancy therapy using genetically engineered drug delivery system

Makoto Sunamura, Dan G. Duda, Hiromune Shimamura, Fuyuhiko Motoi, Toshimasa Yatsuoka, Kazuhiko Shibuya, Kazunori Takeda, Seiki Matsuno

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor dormancy therapy appears useful in treating cancer, but requires that a patient take medication during control of remnant cancer cells. To overcome this inconvenience to patients, drug delivery using genetically engineered cells has become an alternative. Interleukin-12 is both a key regulator of the immune response, particularly that involving CTL and NK cells, and an antiangiogenesis agent. We report the usefulness of the drug delivery of fibroblasts genetically engineered to secrete this cytokine to control angiogenesis in human pancreatic tumors in NK-depleted SCID mice. We evaluate the antiangiogenesis of soluble VEGF receptor (s-flt1) and brain-specific angiogenesis inhibitor 1 (BAI1). Although the in vitro growth of tumor cells was not affected by the presence of IL-12, coinoculation of IL-12 secreting fibroblasts strongly inhibited tumor growth in immunodeficient mice. Neovascularization surrounding the tumor was markedly inhibited where IL-12-secreting fibroblasts were implanted, suppressing tumor growth. Lectin staining in tumor sample sections also showed a significantly reduced number of vessels. The RNA expression of IFN-γ and its inducible antiangiogenic chemokine IP-10 was stimulated in endothelial cells cultured with IL-12. We also found that IL-12 downregulated the expression of endothelial cell mitogens VEGF and bFGF. Antitumor effect and antiangiogenesis of s-flt1 and BAI1 were also demonstrated.

Original languageEnglish
Pages (from-to)425-430
Number of pages6
JournalJapanese Journal of Gastroenterological Surgery
Volume34
Issue number4
DOIs
Publication statusPublished - 2001

Keywords

  • Drug delivery system
  • Pancreatic cancer
  • Tumor dormancy

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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