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P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

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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.

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Abbreviations

CTL:

Cytotoxic T lymphocyte

TAA:

Tumor-associated antigen

ELISPOT:

Enzyme-linked immunospot

MAGE:

Melanoma-associated antigen

hTERT:

Human telomerase reverse transcriptase

WT-1:

Wilms tumor-1

VEGFR:

Vascular endothelial growth factor receptor

PBMC:

Peripheral blood mononuclear cells

PCR:

Polymerase chain reaction

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Acknowledgments

The authors thank Kazumi Fushimi, Maki Kawamura, Nami Nishiyama, and Mikiko Nakamura for their technical assistance.

Conflict of interest

The authors do not have any conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Ishikawa, Japan

    Takeshi Terashima, Eishiro Mizukoshi, Kuniaki Arai, Tatsuya Yamashita, Takashi Kagaya, Masao Honda & Shuichi Kaneko

  2. Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, Kanazawa, 920-8650, Ishikawa, Japan

    Mariko Yoshida & Hajime Ota

  3. Department of Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa, 920-8650, Ishikawa, Japan

    Ichiro Onishi & Masato Kayahara

  4. Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, 920-0934, Ishikawa, Japan

    Koushiro Ohtsubo

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  1. Takeshi Terashima
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  2. Eishiro Mizukoshi
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  3. Kuniaki Arai
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Correspondence to Takeshi Terashima.

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Terashima, T., Mizukoshi, E., Arai, K. et al. P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma. Cancer Immunol Immunother 63, 479–489 (2014). https://doi.org/10.1007/s00262-014-1529-8

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  • DOI: https://doi.org/10.1007/s00262-014-1529-8

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