Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2

Cancer Gene Ther. 2007 Feb;14(2):158-64. doi: 10.1038/sj.cgt.7700994. Epub 2006 Nov 24.


Matrix metalloproteinase-2 (MMP-2) has been used as a target for cancer immunotherapy. The activation of immunization by breaking immune tolerance to self-MMP-2 may be one of the promising approaches for the treatment of MMP-2-positive tumors. In this study, we constructed the xenogeneic tumor cell vaccine c-MMP-2 by transfecting CT26 and LLC cells with chicken MMP-2 cDNA constructs. MMP-2-specific autoantibodies in sera and tumor cells were found in mice immunized with c-MMP-2. Protection against tumor growth was evaluated in respect of the relative contributions of autoantibodies, CD4+, and CD8+ T cells. Treatment with this vaccine (c-MMP-2) also prolonged the survival time of mice bearing cancer. The specific cytotoxic T-cell responses suggested that the treatment increased CD8+ T-cell activity. The antitumor activity of c-MMP-2 was abrogated by in vivo depletion of CD4+ and CD8+ T-lymphocytes and improved by adoptive transfer of CD4+ and CD8+ T-lymphocytes from the mice treated with c-MMP-2. An alternative DNA vaccination strategy for cancer therapy was identified in this study by eliciting humoral and cellular immunoresponse with a crossreacting transfectant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation*
  • Autoantibodies / immunology
  • Base Sequence
  • Blotting, Western
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Chickens
  • Colonic Neoplasms / immunology*
  • DNA Primers
  • DNA, Complementary
  • Immunity, Cellular*
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets
  • Vaccines, DNA / immunology*


  • Autoantibodies
  • Cancer Vaccines
  • DNA Primers
  • DNA, Complementary
  • Vaccines, DNA
  • Matrix Metalloproteinase 2