title: Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination.
abstract: NY-ESO-1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY-ESO-1-expressing tumors with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and showed efficient induction of NY-ESO-1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE-A1, MAGE-A3, MAGE-A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme-linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription-polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY-ESO-1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6-tag and/or bacterial products included in a preparation of CHP-NY-ESO-1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kawada
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wada
authors.forename: Midori
authors.initials: M
authors.lastname: Isobe
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Nami
authors.initials: N
authors.lastname: Okazaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Uenaka
authors.forename: Yurika
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Naoaki
authors.initials: N
authors.lastname: Mizuno
authors.forename: Takashi
authors.initials: T
authors.lastname: Saika
authors.forename: Erika
authors.initials: E
authors.lastname: Ritter
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Roger
authors.initials: R
authors.lastname: Murphy
authors.forename: Ralph
authors.initials: R
authors.lastname: Venhaus
authors.forename: Linda
authors.initials: L
authors.lastname: Pan
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins