Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer

Immunotherapy. 2019 Oct;11(14):1205-1219. doi: 10.2217/imt-2019-0073. Epub 2019 Sep 3.

Abstract

Colorectal cancer is the third commonest malignancy in Asia including Malaysia. The immunogenic cancer-testis antigens, which are expressed in a variety of cancers but with limited expression in normal tissues except the testis, represent an attractive approach to improve treatment options for colorectal cancer. We aimed to validate four PASD1 peptides as the immunotherapeutic targets in colorectal cancer. First, PASD1 mRNA and protein expression were determined via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. The PASD1 peptides specific to HLA-A*24:02 were investigated using IFN-y-ELISpot assay, followed by the cytolytic and granzyme-B-ELISpot assays to analyze the cytolytic effects of CD8+ T cells. Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. CD8+ T cells raised against PASD1(4) peptide were able to lyze HLA-A*24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.

Keywords: HLA-A*2402; cancer-testis antigen; cytotoxic T cell; immunotherapy; peptide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antigens, Neoplasm* / chemistry
  • Antigens, Neoplasm* / immunology
  • Antigens, Neoplasm* / pharmacology
  • Antigens, Nuclear* / chemistry
  • Antigens, Nuclear* / immunology
  • Antigens, Nuclear* / pharmacology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / therapy
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • HCT116 Cells
  • HLA-A24 Antigen / immunology*
  • Humans
  • Immunity, Cellular / drug effects
  • Immunotherapy*
  • Male
  • Neoplasm Proteins* / chemistry
  • Neoplasm Proteins* / immunology
  • Neoplasm Proteins* / pharmacology
  • Peptides* / chemistry
  • Peptides* / immunology
  • Peptides* / pharmacology

Substances

  • Antigens, Neoplasm
  • Antigens, Nuclear
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • Neoplasm Proteins
  • PASD1 protein, human
  • Peptides