Anti-HER2/neu IgG3-(IL-2) and anti-HER2/neu IgG3-(GM-CSF) promote HER2/neu processing and presentation by dendritic cells: implications in immunotherapy and vaccination strategies

Mol Immunol. 2006 Feb;43(6):667-76. doi: 10.1016/j.molimm.2005.04.007.


HER2/neu, a transmembrane glycoprotein overexpressed in several types of human cancers, is a potential target for active immunotherapy. However, this protein and especially its extracellular domain (ECD(HER2)), is weakly immunogenic and is poorly processed by dendritic cells (DCs). Previously, we showed that anti-HER2/neu IgG3-(IL-2) and anti-HER2/neu IgG3-(GM-CSF) fusion proteins can enhance the immunogenicity of ECD(HER2) in mice, and that the non-covalent physical association between each antibody fusion proteins and ECD(HER2) was critical to elicit optimal protective immunity against HER2/neu expressing tumors. We now use the professional antigen-presenting DCs to investigate the effect of the antibody fusion protein binding to ECD(HER2) on its trafficking and presentation. We found that when the extracellular domain of HER2/neu fused to ovalbumin (OVA-ECD(HER2)) is bound by HER2/neu-specific antibody-(IL-2) or antibody-(GM-CSF) fusion proteins, the bound antigen is more efficiently processed by murine bone-marrow-derived dendritic cells (BMDCs) and presented to OVA-specific T-cells than the unbound OVA-ECD(HER2). We also found that ECD(HER2) bound by anti-HER2/neu IgG3-(IL-2) is very efficiently internalized and that the internalized ECD(HER2) is not retained in the early endosomal compartments but traffics to the antigen-processing compartments. These results are consistent with our earlier in vivo studies and suggest that both antibody-(IL-2) and antibody-(GM-CSF) fusion proteins can be used to enhance the immune response to poorly immunogenic antigens including tumor-associated antigens (TAAs).

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antigen Presentation*
  • Antigens, Neoplasm / immunology*
  • Dendritic Cells / immunology*
  • Endosomes
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Immunity
  • Immunoglobulin G
  • Immunotherapy
  • Interleukin-2
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Receptor, ErbB-2 / immunology*
  • Recombinant Fusion Proteins / immunology
  • Vaccination


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Immunoglobulin G
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ovalbumin
  • Receptor, ErbB-2