title: P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.
abstract: Cancer vaccine therapy is one of the most attractive therapies as a new treatment procedure for pancreatic adenocarcinoma. Recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAAs). However, little is known about which TAA and its epitope are the most immunogenic and useful for a cancer vaccine for pancreatic adenocarcinoma. We examined the expression of 17 kinds of TAA in 9 pancreatic cancer cell lines and 12 pancreatic cancer tissues. CTL responses to 23 epitopes derived from these TAAs were analyzed using enzyme-linked immunospot (ELISPOT), CTL, and tetramer assays in 41 patients, and factors affecting the immune responses were investigated. All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3. Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines. The frequency of lymphocyte subsets correlated well with TAA-specific immune response. Overall survival was significantly longer in patients with TAA-specific CTL responses than in those without. P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Ishikawa, Japan, tera@m-kanazawa.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terashima
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Arai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Mariko
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hajime
authors.initials: H
authors.lastname: Ota
authors.forename: Ichiro
authors.initials: I
authors.lastname: Onishi
authors.forename: Masato
authors.initials: M
authors.lastname: Kayahara
authors.forename: Koushiro
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Takashi
authors.initials: T
authors.lastname: Kagaya
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000401:mortality; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality; D060888:Real-Time Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D040301:Vascular Endothelial Growth Factor Receptor-2; C509186:TERT protein, human; D019098:Telomerase