Immunological evaluation of a novel HLA-A2 restricted phosphopeptide of tumor associated Antigen, TRAP1, on cancer therapy

Vaccine: X
Min-Han LinWang-Chou Sung

Abstract

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 presente...Continue Reading

Citations

Dec 19, 2019·Molecular & Cellular Proteomics : MCP·Marthe SollederDavid Gfeller
Aug 9, 2020·Nature Reviews. Drug Discovery·Alexandre HarariLana E Kandalaft
Jan 12, 2021·Frontiers in Immunology·Robin MinatiPierre Thibault
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Marthe SollederDavid Gfeller

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Methods Mentioned

BETA
transgenic
electrophoresis
Protein Assay
immunoprecipitation
flow cytometry
FCS

Software Mentioned

MASCOT
Proteome Discoverer
FCS Express
NetMHC

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