Validation of immunogenic PASD1 peptides against HLA-A24:02 colorectal cancer

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 color...

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Bibliographic Details
Published in:Immunotherapy 2019-10, Vol.11 (14), p.1205-1219
Main Authors: Soh, Joanne EC, Abu, Nadiah, Sagap, Ismail, Mazlan, Luqman, Yahaya, Azyani, Mustangin, Muaatamarulain, Khoo, Tze S, Saidin, Sazuita, Ishak, Muhiddin, Ab Mutalib, Nurul S, Jamal, Rahman
Format: Article
Language:English
Subjects:
Antigens
Apoptosis
Cancer
Cancer therapies
cancer-testis antigen
CD8 antigen
Colorectal cancer
Colorectal carcinoma
cytotoxic T cell
Cytotoxicity
Enzyme-linked immunosorbent assay
Gene expression
Histocompatibility antigen HLA
HLA-A2402
Immunogenicity
Immunohistochemistry
Immunotherapy
Interferon
Laboratories
Ligands
Lymphocytes T
Malignancy
Medical prognosis
mRNA
peptide
Peptides
Polymerase chain reaction
Proteins
Tumors
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Summary: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.
ISSN:1750-743X
1750-7448
DOI:10.2217/imt-2019-0073