The
CHP-HER2 vaccine, comprising truncated 146HER2
protein complexed with
nanogels of cholesteryl
pullulan (CHP), is a novel
protein antigen vaccine that elicits 146HER2-specific CD8(+) and CD4(+) T-cell immune responses in patients with HER2-expressing
tumors. We analyzed the humoral responses in patients vaccinated with CHP-HER2 and those with CHP-HER2 plus
granulocyte-macrophage colony-stimulating factor (
GM-CSF). The
vaccine was injected subcutaneously at a dose of 300 microg
protein. Nine patients received the
vaccine alone over the first four
injections, followed by CHP-HER2 with
GM-CSF or
OK-432, whereas six received CHP-HER2 plus
GM-CSF from the first cycle. 146HER2-specific
IgG antibodies were induced in 14 patients, who were negative at baseline. The
antibodies became detectable after the second or third vaccination and reached plateau levels after the third or fourth cycle in patients vaccinated with CHP-HER2 plus
GM-CSF. In contrast, the
antibodies appeared only after the third to sixth vaccination and the plateau appeared after the fourth to eighth cycle in patients vaccinated with the
CHP-HER2 vaccine alone over the first four cycles. The
antibodies induced by the
vaccine were not reactive with HER2
antigen expressed on the cell surface in any of the patients.
Epitope analysis using overlapping
peptides revealed a single region in the 146HER2
protein,
amino acids 127-146, in eight patients who were initially vaccinated with CHP-HER2 alone. Similarly, the same HER2 region was recognized dominantly in patients vaccinated with
GM-CSF. Our results indicate that CHP-HER2 induced HER2-specific humoral responses in patients with HER2-expressing
tumors and that
GM-CSF seems to accelerate the responses.