Dendritic cells pulsed with an anti-idiotype antibody mimicking Her-2/neu induced protective antitumor immunity in two lines of Her-2/neu transgenic mice

Cell Immunol. 2010;263(1):9-21. doi: 10.1016/j.cellimm.2010.02.010. Epub 2010 Feb 24.

Abstract

Her-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. To test the efficacy of immune-based strategies in eliciting an antitumor response, we have evaluated the vaccine potential of an anti-idiotype (Id) antibody, 6D12 in tolerant hosts. Immunization of human Her-2/neu transgenic mice with 6D12-pulsed dendritic cells (DC) could reverse Her-2/neu unresponsiveness and result in the induction of Her-2/neu-specific humoral and cellular immune responses and protection against tumors expressing Her-2/neu. Furthermore, the tumor rejection in 6D12-pulsed DC immunized mice was associated with development of memory response. Vaccination of transgenic female FVB-neuN mice that carry the rat Her-2/neu oncogene, markedly delayed tumor onset and developed significantly fewer spontaneous mammary tumors compared with mice treated with control vaccine. Tumor growth inhibition was associated with the induction of Her-2/neu-specific immune responses. These data suggest the potential use of anti-Id antibody 6D12 as a vaccine for immunotherapy of Her-2/neu-positive human cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / metabolism*
  • Antigen Presentation
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Cancer Vaccines*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Humans
  • Immunity, Innate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Mimicry
  • Neoplasm Transplantation
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / metabolism
  • Transfection

Substances

  • Antibodies, Anti-Idiotypic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • ERBB2 protein, human
  • Receptor, ErbB-2