Xu Wei, Li Hui-Zhong, Liu Jun-Jie, Guo Zhen, Zhang Bao-Fu, Chen Fei-Fei, Pei Dong-Sheng, Zheng Jun-Nian
Laboratory of Biological Cancer Therapy, Surgical oncology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
Tumour Biol. 2011 Feb;32(1):63-9. doi: 10.1007/s13277-010-0098-5. Epub 2010 Aug 16.
Peptide-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and prolong survival in patients with various cancers. Protein antigens and their specific epitopes are formulation targets for anti-tumor vaccines. Bioinformatical approaches to predict major histocompatibility complex binding peptides can facilitate the resource-consuming effort of T cell epitope identification. Proliferating cell nuclear antigen including Ki-67 and PCNA, associated with the proliferation process of the cell, seems to be an attractive new target for tumor-specific immunotherapy. In this study, we predicted seven HLA-A0201-restricted CTL candidate epitope of Ki-67 and eight epitope of PCNA by computer algorithm SYFPEITHI, BIMAS, and IEDB_ANN. Subsequently, biological functions of these peptides were tested by experiments in vitro. We found Ki-67((280-288)) (LQGETQLLV) had the strongest binding-affinity with HLA-A0201. Further study revealed that Ki-67((280-288)) increased the frequency of IFN-γ-producing T cells compared to a negative peptide. Because Ki-67 was broadly expressed in most advanced malignant tumors, indicating a potential anti-tumor application in the future.
基于肽的免疫治疗策略作为一种成功诱导抗肿瘤免疫反应并延长各种癌症患者生存期的方法，似乎很有前景。蛋白质抗原及其特异性表位是抗肿瘤疫苗的制剂靶点。预测主要组织相容性复合体结合肽的生物信息学方法可以促进T细胞表位鉴定这一耗费资源的工作。包括Ki-67和PCNA在内的增殖细胞核抗原与细胞增殖过程相关，似乎是肿瘤特异性免疫治疗的一个有吸引力的新靶点。在本研究中，我们通过计算机算法SYFPEITHI、BIMAS和IEDB_ANN预测了Ki-67的七个HLA-A0201限制性CTL候选表位和PCNA的八个表位。随后，通过体外实验测试了这些肽的生物学功能。我们发现Ki-67（(280 - 288)）（LQGETQLLV）与HLA-A0201的结合亲和力最强。进一步研究表明，与阴性肽相比，Ki-67（(280 - 288)）增加了产生IFN-γ的T细胞频率。由于Ki-67在大多数晚期恶性肿瘤中广泛表达，表明其在未来具有潜在的抗肿瘤应用价值。
