Anti-tumor immunity induced by interleukin-12 gene therapy in a metastic model of breast cancer is mediated by natural killer cells

Celia M. Divino, Shu Hsia Chen, Wen Yang, Swan Thung, Steven T. Brower, Savio L.C. Woo

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

An intrahepatic tumor model for metastatic breast cancer was generated in syngeneic mice by direct inoculation of JC cells, a murine mammary adenocarcinoma cell line. Intratumoral administration of a recombinant adenoviral vector expressing the murine Interleukin-12 (ADV-mIL-12) resulted in significant reduction in the tumor volume compared to control vector. Tumor regression was also evident on histopathologic analysis of the liver, where inflammatory changes as opposed to nuclear atypia predominated after IL-12 vector treatment. There was a significant prolongation in the long term survival of IL-12 treated animals, with complete tumor rejection in 40% of the animals. In vivo depletion studies using specific monoclonal antibodies against the various lymphocyte subsets showed a significant reduction in long term survival after natural killer (NK) cell depletion. This suggests that the NK cell is a critical effector in the antitumor effect mediated by IL-12. These results strongly support the potential role of gene mediated cytokine therapy for the treatment of metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)129-134
Number of pages6
JournalBreast Cancer Research and Treatment
Volume60
Issue number2
DOIs
StatePublished - 2000

Keywords

  • Adrenoviral vector
  • Gene therapy
  • Immunotherapy
  • Interleukin-12
  • NK cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Anti-tumor immunity induced by interleukin-12 gene therapy in a metastic model of breast cancer is mediated by natural killer cells'. Together they form a unique fingerprint.

Cite this