Autor: |
Min-Han Lin, Kuan-Yin Shen, Bing-Sin Liu, I-Hua Chen, Yuh-Pyng Sher, Guan-Chin Tseng, Shih-Jen Liu, Wang-Chou Sung |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
|
Zdroj: |
Vaccine: X, Vol 1, Iss , Pp - (2019) |
Druh dokumentu: |
article |
ISSN: |
2590-1362 |
DOI: |
10.1016/j.jvacx.2019.100017 |
Popis: |
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. Keywords: TRAP1, HLA-A2, Phosphopeptide, Cytotoxic T lymphocyte, Immunotherapy, Cancer vaccine |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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