title: Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.
abstract: We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3 . WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients.
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Iwai
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kagawa
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Neurosurgery, Kinki University, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.affiliation: Cell Signal Unit, Okinawa Institute of Science and Technology, Okinawa, Japan.
authors.forename: Olga
authors.initials: O
authors.lastname: Elisseeva
authors.affiliation: Department of Hematology, Tohoku University, Miyagi, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ichinohasama
authors.affiliation: Tokai Central Hospital, Aichi, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Respiratory Medicine and Allergy, Rheumatic Disease, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Respiratory Medicine and Allergy, Rheumatic Disease, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nakae
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakata
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.affiliation: Respiratory Medicine and Allergy, Rheumatic Disease, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujiki
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Soyoko
authors.initials: S
authors.lastname: Morimoto
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|Respiratory Medicine and Allergy, Rheumatic Disease, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Immunopathology, Immunology Frontier Research Center (World Premier International Research Center), Osaka University, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005909:Glioblastoma / Q000276:immunology* / Q000401:mortality* / Q000628:therapy; D059871:HLA-A24 Antigen / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014611:Vaccination; D025721:WT1 Proteins / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019496:Cancer Vaccines; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D010455:Peptides; D025721:WT1 Proteins
keywords: WT1 IgG antibody; WT1 peptide-based immunotherapy; glioblastoma; predictive marker