國家衛生研究院 NHRI:Item 3990099045/11856
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    題名: Immunological evaluation of a novel HLA-A2 restricted phosphopeptide of tumor associated Antigen, TRAP1, on cancer therapy
    作者: Lin, MH;Shen, KY;Liu, BS;Chen, IH;Sher, YP;Tseng, GC;Liu, SJ;Sung, WC
    貢獻者: National Institute of Infectious Diseases and Vaccinology
    摘要: The tumor necrosis factor receptor associated protein 1 (TRAP1) is a mitochondria chaperon protein that has been previously implicated as a target for cancer therapy due to its expression level is linked to tumor progression. In this study, an immunodominant phosphopeptide of TRAP1 was identified from an HLA-A2 gene transfected mouse cancer cell line using mass spectrometry, and a synthetic phosphopeptide was generated to evaluate the potency on cancer immunotherapy. In the transporter associated with antigen processing (TAP) deficient cell, the conjugated phosphate group plays a critical role to enhance the binding affinity of phosphopeptide with HLA-A2 molecule. On the basis of immunological assay, immunization of synthetic phosphopeptide could induce a high frequency of IFN-γ-secreting CD8 + T cells in HLA-A2 transgenic mice, and the stimulated cytotoxic T lymphocytes showed a high target specificity to lysis the epitope-pulsed splenocytes in vivo and the human lung cancer cell in vitro. In a tumor challenge assay, vaccination of the HLA-A2 restricted phosphopeptide appeared to suppress the tumor growth and prolong the survival period of tumor-bearing mice. These results suggest that novel phosphopeptide is naturally presented as a HLA-A2-restricted CTL epitope and capable of being a potential candidate for the development of therapeutic vaccine against high TRAP1-expressing cancers.
    日期: 2019-04-11
    關聯: Vaccine: X. 2019 Apr 11;1:Article number 100017.
    Link to: http://dx.doi.org/10.1016/j.jvacx.2019.100017
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85063203868
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