Tsukagoshi Mariko, Wada Satoshi, Hirono Seiko, Yoshida Shintaro, Yada Erica, Sasada Tetsuro, Shirabe Ken, Kuwano Hiroyuki, Yamaue Hiroki
Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi Gunma 371-8511, Japan.
Department of Innovative Cancer Immunotherapy, Gunma University Graduate School of Medicine, Maebashi Gunma 371-8511, Japan.
Oncotarget. 2018 Jul 31;9(59):31448-31458. doi: 10.18632/oncotarget.25837.
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-A2402. 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-A2402-positive pancreatic cancer cells that endogenously expressed mesothelin. These results indicate that the mesothelin-10-5 peptide is a novel HLA-A2402 restricted CTL epitope and that it is a promising candidate target for antigen-specific immunotherapy against pancreatic cancers.
胰腺癌是一种高度恶性的肿瘤，开发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，在侵袭和迁移过程中起重要作用。在本研究中，我们聚焦于间皮素作为胰腺癌疫苗的肿瘤特异性抗原靶点。我们首先研究了受HLA - A2402限制的间皮素衍生表位肽。总共合成了19种候选肽，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。5种源自间皮素的肽诱导出了肽特异性CTL，并且这些CTL成功表现出肽特异性γ干扰素产生。在每种CTL扩增后，建立了两条CTL系，它们由间皮素 - 10 - 5肽（AFYPGYLCSL）诱导产生。这些CTL系表现出肽特异性细胞毒性和γ干扰素产生。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 - A2402阳性胰腺癌细胞也具有特异性细胞毒性活性。这些结果表明，间皮素 - 10 - 5肽是一种新型的受HLA - A2402限制的CTL表位，并且它是针对胰腺癌进行抗原特异性免疫治疗的一个有前景的候选靶点。
