UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Immunotherapy. 2019 Oct;11(14):1205-1219. doi: 10.2217/imt-2019-0073. Epub 2019 Sep 3.
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-A24:02 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-A24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.
结直肠癌是亚洲（包括马来西亚）第三大常见恶性肿瘤。免疫原性的癌症睾丸抗原在多种癌症中表达，但在正常组织中除睾丸外表达有限，这代表了改善结直肠癌治疗选择的一种有吸引力的方法。我们旨在验证四个 PASD1 肽作为结直肠癌的免疫治疗靶点。首先，通过实时聚合酶链反应（RT-PCR）和免疫组织化学测定 PASD1 mRNA 和蛋白表达。使用 IFN-y-ELISpot 测定法研究 PASD1 肽与 HLA-A24:02 的特异性，然后进行细胞溶解和 granzyme-B-ELISpot 测定法以分析 CD8 T 细胞的细胞溶解作用。PASD1 的基因和蛋白表达分别在 20%和 17.3%的结直肠癌样本中检测到。PASD1(4) 肽在结直肠癌样本中显示出免疫原性。针对 PASD1(4) 肽产生的 CD8 T 细胞能够溶解 HLA-A24:02+PASD1+细胞。我们的结果表明，PASD1(4) 肽代表了结直肠癌的一个潜在靶点。
