Humoral immune responses in patients vaccinated with 1-146 HER2 protein complexed with cholesteryl pullulan nanogel.
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.
Kageyama
Shinichi
S
Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Kitano
Shigehisa
S
Hirayama
Michiko
M
Nagata
Yasuhiro
Y
Imai
Hiroshi
H
Shiraishi
Taizo
T
Akiyoshi
Kazunari
K
Scott
Andrew M
AM
Murphy
Roger
R
Hoffman
Eric W
EW
Old
Lloyd J
LJ
Katayama
Naoyuki
N
Shiku
Hiroshi
H
D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood*; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C528170:CHP-HER2 vaccine