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Expression of tumor rejection antigens in colorectal carcinomas
Teruo Sasatomi1, Yuichi Suefuji, Kazuko Matsunaga
1Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan. sasatomi@med.kurume-u.ac.jp
Background:
The authors recently reported that the SART2 and SART3 antigens encode tumor epitopes recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) established from esophageal carcinoma patients. The current study investigated these antigens to explore a potential molecule for specific immunotherapy for colorectal carcinoma patients.
Methods:
The SART2 and SART3 antigens were investigated by Western blotting in colorectal carcinoma cell lines and in cancer tissues. For induction of CTLs, peripheral blood mononuclear cells (PBMCs) of HLA A-24-positive cancer patients were stimulated in vitro with peptides.
Results:
The 140 kD SART3 antigen was expressed in both the cytosol and nuclear fractions of all six colon carcinoma cell lines, 27 of 41 (65.9%) cytosol fractions, 30 of 41 (73.2%) nuclear fractions of colorectal carcinoma tissue samples, and in 0 of 7 non-tumorous tissues. The 100 kD SART2 antigen was expressed in the cytosol fractions of 2 of 6 colon carcinoma cell lines, 5 of 20 (25%) cytosol fractions of colorectal carcinoma tissue samples, and in 0 of 7 non tumorous tissues. HLA-A24-restricted CTLs cytotoxic to colon carcinoma cells were induced from PBMCs of colon carcinoma patients by stimulation with the two immunogenic peptides of SART3.
Conclusions:
The SART3 antigen could be an appropriate target molecule for specific immunotherapy for colorectal carcinoma patients.
Insights
The SART3 antigen is highly expressed in colorectal carcinoma tissues and can be targeted for specific immunotherapy. This study demonstrates its potential as a therapeutic target for colon cancer patients.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- SART2 and SART3 antigens identified as tumor epitopes recognized by HLA-A24-restricted cytotoxic T lymphocytes (CTLs) in esophageal carcinoma.
- Previous research established SART2 and SART3 as targets for tumor-specific CTLs.
Purpose of the Study:
- Investigate SART2 and SART3 antigens as potential targets for specific immunotherapy in colorectal carcinoma.
- Determine the expression patterns of SART2 and SART3 in colorectal cancer.
Main Methods:
- Western blotting used to analyze SART2 and SART3 antigen expression in colorectal carcinoma cell lines and tissues.
- Peripheral blood mononuclear cells (PBMCs) from HLA-A24-positive patients stimulated in vitro with peptides to induce CTLs.
Main Results:
- SART3 antigen (140 kD) showed significant expression in colorectal carcinoma cell lines and tissues (65.9% cytosol, 73.2% nuclear), with no expression in non-tumorous tissues.
- SART2 antigen (100 kD) was expressed in a subset of colorectal carcinoma cell lines and tissues (25% cytosol), but not in non-tumorous tissues.
- HLA-A24-restricted CTLs targeting colon carcinoma cells were successfully induced using SART3-derived peptides.
Conclusions:
- SART3 antigen demonstrates high specificity and expression in colorectal carcinoma, making it a promising target for immunotherapy.
- The findings support the development of SART3-based immunotherapies for colorectal cancer patients.