HLA-A2-restricted Cytotoxic T Lymphocyte Epitopes from Human Hepsin as Novel Targets for Prostate Cancer Immunotherapy

Authors

  • J. Guo,

    1. The Research Center of Stem Cell, Tissue and Organ Engineering, Kunming General Hospital of PLA, Kunming, China
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  • G. Li,

    1. Department of Hepatobiliary Surgery, The First People's Hospital of Liangshan Prefecture, Sichuan, China
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  • J. Tang,

    1. Department of Gastroenterology, the 105th hospital of Nanjing Military Command, Hefei, Anhui Province, China
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  • X.-B. Cao,

    1. The Research Center of Stem Cell, Tissue and Organ Engineering, Kunming General Hospital of PLA, Kunming, China
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  • Q.-Y. Zhou,

    1. Department of Urinary Surgery, Kunming General Hospital of PLA, Yunnan, China
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  • Z.-J. Fan,

    1. The Research Center of Stem Cell, Tissue and Organ Engineering, Kunming General Hospital of PLA, Kunming, China
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  • B. Zhu,

    Corresponding author
    1. Department of Gastroenterology, the 105th hospital of Nanjing Military Command, Hefei, Anhui Province, China
    • Correspondence to: B. Zhu, M.D., Department of Gastroenterology, the 105th hospital of Nanjing Military Command, Hefei 230031, Anhui Province, China. E-mail: binzhu105@yeah.net or X. -H. Pan, M.D., The Research Center of Stem Cell, Tissue and Organ Engineering, Kunming General Hospital of Chendu Military Command, Kunming 650032, Yunnan Province, China. E-mail: xinghuapan@yahoo.com.cn

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  • X.-H. Pan

    Corresponding author
    1. The Research Center of Stem Cell, Tissue and Organ Engineering, Kunming General Hospital of PLA, Kunming, China
    • Correspondence to: B. Zhu, M.D., Department of Gastroenterology, the 105th hospital of Nanjing Military Command, Hefei 230031, Anhui Province, China. E-mail: binzhu105@yeah.net or X. -H. Pan, M.D., The Research Center of Stem Cell, Tissue and Organ Engineering, Kunming General Hospital of Chendu Military Command, Kunming 650032, Yunnan Province, China. E-mail: xinghuapan@yahoo.com.cn

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  • Jun Guo, Guo Li and Jun Tang contributed equally to this work.

Abstract

Hepsin is a type II transmembrane serine protease that is overexpressed in prostate cancer, and it is associated with prostate cancer cellular migration and invasion. Therefore, HPN is a biomarker for prostate cancer. CD8+ T cells play an important role in tumour immunity. This study predicted and identified HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes in human hepsin protein. HLA-A2-restricted CTL epitopes were identified using the following four-step procedure: (1) a computer program generated predicted epitopes from the amino acid sequence of human hepsin; (2) an HLA-A2-binding assay detected the affinity of the predicted epitopes to the HLA-A2 molecule; (3) the primary T cell response against the predicted epitopes was stimulated in vitro; and (4) the induced CTLs towards different types of hepsin- or HLA-A2-expressing prostate cancer cells were detected. Five candidate peptides were identified. The effectors that were induced by human hepsin epitopes containing residues 229 to 237 (Hpn229; GLQLGVQAV), 268 to 276 (Hpn268; PLTEYIQPV) and 191 to 199 (Hpn199; SLLSGDWVL) effectively lysed LNCaP prostate cancer cells that were hepsin-positive and HLA-A2 matched. These peptide-specific CTLs did not lyse normal liver cells with low hepsin levels. Hpn229, Hpn268 and Hpn199 increased the frequency of IFN-γ-producing T cells compared with the negative peptide. These results suggest that the Hpn229, Hpn268 and Hpn199 epitopes are novel HLA-A2-restricted CTL epitopes that are capable of inducing hepsin-specific CTLs in vitro. Hpn229, Hpn268 and Hpn199 peptide-based vaccines may be useful for immunotherapy in patients with prostate cancer.

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