Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients.
NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY-ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody-negative and 2 patients were positive prior to vaccination. Vaccination with CHP-NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO-1 antibody-positive cancer patients. A peptide spanning amino acids 91-108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO-1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1.
Kawabata
Ryohei
R
Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Wada
Hisashi
H
Isobe
Midori
M
Saika
Takashi
T
Sato
Shuichiro
S
Uenaka
Akiko
A
Miyata
Hiroshi
H
Yasuda
Takushi
T
Doki
Yuichiro
Y
Noguchi
Yuji
Y
Kumon
Hiromi
H
Tsuji
Kazuhide
K
Iwatsuki
Keiji
K
Shiku
Hiroshi
H
Ritter
Gerd
G
Murphy
Roger
R
Hoffman
Eric
E
Old
Lloyd J
LJ
Monden
Morito
M
Nakayama
Eiichi
E
D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002784:Cholesterol / Q000008:administration & dosage* / Q000276:immunology; D018604:Epitope Mapping / Q000379:methods; D005936:Glucans / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D014611:Vaccination / Q000379:methods*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D005936:Glucans; D007074:Immunoglobulin G; D008565:Membrane Proteins; C009109:pullulan; D002784:Cholesterol