Antitumor effect by interleukin-11 receptor alpha-locus chemokine/CCL27, introduced into tumor cells through a recombinant adenovirus vector

Cancer Res. 2003 Aug 1;63(15):4420-5.

Abstract

In this study, we examined antitumor activity of a mouse CC chemokine ILC/CCL27 and a mouse CX(3)C chemokine fractalkine/CX(3)CL1 in vivo. We generated recombinant adenovirus vectors with a fiber mutation, encoding mILC (Ad-RGD-mILC) and mFKN (Ad-RGD-mFKN). We confirmed tumor cells infected with Ad-RGD-mILC and Ad-RGD-mFKN to express and release these chemokines. Tumor rejection experiments in vivo were carried out by inoculating OV-HM cells infected with Ad-RGD-mILC or Ad-RGD-mFKN into immunocompetent mice. mILC significantly suppressed the tumor growth, whereas no such significant effect was observed by mFKN. The antitumor activity induced by mILC was T cell dependent, involving both CD4(+) and CD8(+) T cells. Immunohistochemical analysis revealed accumulation of both CD3(+) lymphocytes and NK cells in the tumor tissue transduced with mILC and mFKN. However, there was a significant difference in the distribution of infiltrating cells. Furthermore, mFKN appeared to have an angiogenic activity, which might have masked its tumor suppressive activity. Collectively, ILC/CCL27 may be a good candidate molecule for cancer gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Chemokine CCL27
  • Chemokine CX3CL1
  • Chemokines, CC / genetics*
  • Chemokines, CC / immunology
  • Chemokines, CX3C / genetics*
  • Chemokines, CX3C / immunology
  • Female
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Humans
  • Immunization, Passive / methods
  • Killer Cells, Natural / immunology
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy*

Substances

  • CCL27 protein, human
  • CX3CL1 protein, human
  • Ccl27a protein, mouse
  • Chemokine CCL27
  • Chemokine CX3CL1
  • Chemokines, CC
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • Membrane Proteins