Vaccination with novel combinations of anti-HER2/neu cytokines fusion proteins and soluble protein antigen elicits a protective immune response against HER2/neu expressing tumors

Vaccine. 2006 Jan 16;24(3):304-16. doi: 10.1016/j.vaccine.2005.07.073. Epub 2005 Aug 10.


We have previously demonstrated that anti-HER2/neu IgG3-(IL-2), (IL-12)-IgG3, or IgG3-(GM-CSF) antibody fusion proteins (mono-AbFPs) elicit anti-tumor activity against murine tumors expressing HER2/neu when used as adjuvants of extracellular domain of HER2/neu (ECD(HER2)) protein vaccination. We have now studied the effect of combinations of IL-2 and IL-12 or IL-12 and GM-CSF mono-AbFPs during vaccination with ECD(HER2). In addition, we developed two novel anti-HER2/neu IgG3-cytokine fusion proteins in which IL-2 and IL-12 or IL-12 and GM-CSF were fused to the same IgG3 molecule (bi-AbFPs). (IL-12)-IgG3-(IL-2) and (IL-12)-IgG3-(GM-CSF) were properly assembled and retained both cytokine activity and the ability to bind antigen. Vaccination of mice with ECD(HER2) and a combination of cytokines as either bi-AbFPs or two mono-AbFPs activated both Thl and Th2 immune responses and resulted in significant protection against challenge with a HER2/neu expressing tumor. Our results suggest that this approach will be effective in the prevention and/or treatment of HER2/neu expressing tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies / chemistry
  • Antibodies / genetics
  • Antibodies / immunology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Extracellular Space / metabolism
  • Genes, erbB-2 / genetics*
  • Genes, erbB-2 / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin G / immunology
  • Interleukin-12 / immunology
  • Interleukin-12 / pharmacology
  • Interleukin-2 / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / prevention & control*
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / immunology*
  • Transfection
  • Vaccination


  • Adjuvants, Immunologic
  • Antibodies
  • Cancer Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor