Identification of a novel HLA-A24-restricted cytotoxic T lymphocyte epitope peptide derived from mesothelin in pancreatic cancer.
Identification of a novel HLA-A24-restricted cytotoxic T lymphocyte epitope peptide derived from mesothelin in pancreatic cancer.
复制标题
鉴定出新型的HLA-A24限制性细胞毒性T淋巴细胞表位肽，该肽在胰腺癌中衍生自中皮素。
DOI：
10.18632/oncotarget.25837
复制
发表时间：
2018-07-31
期刊：
影响因子：
--
通讯作者：
Yamaue H
中科院分区：
文献类型：
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作者：
Tsukagoshi M;Wada S;Hirono S;Yoshida S;Yada E;Sasada T;Shirabe K;Kuwano H;Yamaue H
胰腺癌涉及高度恶性肿瘤，发展新的治疗策略至关重要。间皮素在浸润性胰腺癌细胞中过表达，在浸润和迁移过程中起重要作用。在这项研究中，我们关注间皮素作为胰腺癌疫苗的肿瘤特异性抗原靶点。我们首先研究了限制于HLA-A*2402的间皮素来源的表位肽。总共合成了19个候选肽，然后我们确定了它们诱导肽特异性细胞毒性T淋巴细胞（ctl）的潜力。肽特异性ctl是由源自间皮素的五种肽诱导的，这些ctl成功地表现出肽特异性IFN-γ的产生。每个CTL扩增后，建立2个间皮素-10-5肽（AFYPGYLCSL）诱导的CTL系。这些CTL表现出肽特异性的细胞毒性和IFN-γ的产生。此外，我们能够生成间皮素-10-5肽特异性CTL克隆。这些CTL克隆对内源性表达间皮素的HLA-A*2402阳性胰腺癌细胞也具有特异性的细胞毒活性。这些结果表明，间皮素-10-5肽是一个新的HLA-A*2402限制性CTL表位，是胰腺癌抗原特异性免疫治疗的一个有希望的候选靶点。
Pancreatic cancer involves highly malignant tumors, and the development of new therapeutic strategies is critical. Mesothelin is overexpressed in infiltrating pancreatic cancer cells and plays an important role in the invasion and migration processes. In this study, we focused on mesothelin as a tumor-specific antigen target for a pancreatic cancer vaccine. We first investigated the mesothelin-derived epitope peptide restricted to HLA-A*2402. A total of 19 candidate peptides were synthesized, and we then determined their potential to induce peptide-specific cytotoxic T lymphocytes (CTLs). Peptide-specific CTLs were induced by five peptides derived from mesothelin, and these CTLs successfully exhibited peptide-specific IFN-γ production. After the expansion of each CTL, two CTL lines were established, which were induced by mesothelin-10-5 peptide (AFYPGYLCSL). These CTL lines exhibited peptide-specific cytotoxicity and IFN-γ production. Moreover, we were able to generate mesothelin-10-5 peptide-specific CTL clones. These CTL clones also had specific cytotoxic activity against HLA-A*2402-positive pancreatic cancer cells that endogenously expressed mesothelin. These results indicate that the mesothelin-10-5 peptide is a novel HLA-A*2402 restricted CTL epitope and that it is a promising candidate target for antigen-specific immunotherapy against pancreatic cancers.