Combined CXC chemokine and interleukin-12 gene transfer enhances antitumor immunity

Gene Ther. 2001 Feb;8(4):282-90. doi: 10.1038/


It has been shown that intratumor administration of an adenovirus vector expressing IL-12 produces a potent T cell-mediated response that leads to significant tumor regression in a murine breast cancer model. IP-10 and MIG are CXC chemokines that recruit mononuclear cells in vivo. In addition to their chemotactic roles, IP-10 and MIG inhibit angiogenesis. We tested whether the addition of IP-10 or MIG may both enhance the antitumor immune response of IL-12 through T cell recruitment and inhibit tumor growth through angiostasis. Adenovirus vectors expressing IP-10 or MIG and/or IL-12 were administered intratumorally in a murine model of mammary adenocarcinoma and fibrosarcoma. Administration of IP-10 or MIG in combination with IL-12 resulted in considerable tumor regression and increased survival time of tumor-bearing animals as compared with IP-10, MIG, IL-12 alone or control-treated animals, with the IP-10 IL-12 combination being most effective. These results suggest augmenting the antitumor immune response and inhibiting tumor angiogenesis with adenoviral vectors expressing IP-10 in combination with IL-12 is a novel way to enhance tumor regression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Blotting, Northern
  • CD3 Complex / analysis
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Chemokines, CXC / genetics*
  • Collagen
  • Cytotoxicity Tests, Immunologic
  • Drug Combinations
  • Endothelium, Vascular / pathology
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Injections, Intralesional
  • Interferon-gamma / analysis
  • Interleukin-12 / genetics*
  • Interleukin-4 / analysis
  • Laminin
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Nude
  • Neovascularization, Pathologic
  • Proteoglycans
  • T-Lymphocytes / immunology
  • Xenograft Model Antitumor Assays


  • CD3 Complex
  • Chemokines, CXC
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • Fibroblast Growth Factor 2
  • matrigel
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Collagen