Insights into the mechanism of anti-tumor immunity in mice vaccinated with the human HER2/neu extracellular domain plus anti-HER2/neu IgG3-(IL-2) or anti-HER2/neu IgG3-(GM-CSF) fusion protein

In the present study, we demonstrate that a physical association between the extracellular domain of human HER2/neu receptor (ECDHER2) plus anti-HER2/neu IgG3-(IL-2) or anti-HER2/neu IgG3-(GM-CSF) was required to elicit the most effective anti-tumor immune response against a syngeneic tumor expressing rat HER2/neu. Immune effectors including CD4+, CD8+, and NK cells contributed to protection against tumor growth. Vaccinated B-cell deficient mice did not elicit tumor protection, suggesting a critical role for B-cells in a protective immune response. These results provide insights into the mechanisms responsible for the protective tumor immunity elicited when antibody-(IL-2 or GM-CSF) are used as enhancers of vaccines targeting tumor antigens.