RRC ID 44970
著者 Terashima T, Mizukoshi E, Arai K, Yamashita T, Yoshida M, Ota H, Onishi I, Kayahara M, Ohtsubo K, Kagaya T, Honda M, Kaneko S.
タイトル P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.
ジャーナル Cancer Immunol Immunother
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.
巻・号 63(5)
ページ 479-89
公開日 2014-5-1
DOI 10.1007/s00262-014-1529-8
PMID 24633336
MeSH Adenocarcinoma / immunology* Adenocarcinoma / mortality Aged Antigens, Neoplasm / immunology* Cancer Vaccines / immunology* Epitopes, T-Lymphocyte / immunology Female Flow Cytometry Humans Kaplan-Meier Estimate Male Pancreatic Neoplasms / immunology* Pancreatic Neoplasms / mortality Real-Time Polymerase Chain Reaction T-Lymphocytes, Cytotoxic / immunology Telomerase / immunology Tumor Suppressor Protein p53 / immunology Vascular Endothelial Growth Factor Receptor-2 / immunology
IF 5.442
引用数 12
WOS 分野 ONCOLOGY IMMUNOLOGY
リソース情報
ヒト・動物細胞 PK-1(RCB1972)