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CD133表位联合热休克蛋白佐剂疫苗引发抗白血病的免疫应答
引用本文:王硕,范红霞,李杨,郑华国,李鑫,李长菲,陈立钊,鞠莹,孟颂东.CD133表位联合热休克蛋白佐剂疫苗引发抗白血病的免疫应答[J].生物工程学报,2017,33(6):1006-1017.
作者姓名:王硕  范红霞  李杨  郑华国  李鑫  李长菲  陈立钊  鞠莹  孟颂东
作者单位:1 河北大学 生命科学学院,河北 保定 071002,2 天津医科大学 基础医学院,天津 300070,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101,3 中国科学院微生物研究所 中国科学院病原微生物与免疫学重点实验室,北京 100101; 4 中国科学院大学 生命科学学院,北京 100049
基金项目:国家重点基础研究发展计划 (973计划) (No. 2014CB542602),国家自然科学基金 (Nos. 31230026, 81321063, 81471960, 81402840, 81672815) 资助。
摘    要:肿瘤干细胞具有肿瘤形成、自我更新和抗化疗的特性,因而受到广泛关注和研究。CD133作为重要的肿瘤干细胞标志物与肿瘤细胞的干性与恶性密切相关。本研究筛选并且鉴定了CD133的3个H2-Kd限制性的细胞毒性T细胞 (CTL) 的表位,分别是CD133419–428、CD133702–710和CD133760–769。将重组热休克蛋白gp96为佐剂联合CD133表位制备表位疫苗,将疫苗免疫CD133+白血病移植的小鼠后引发抗肿瘤的特异性T细胞免疫应答。转输CD133表位特异的T细胞同样可以抑制小鼠淋巴瘤的生长。该研究为设计抗CD133+的白血病和其他肿瘤的表位疫苗提供了依据。

关 键 词:CD133,表位,gp96,白血病,细胞毒性T细胞
收稿时间:2016/12/15 0:00:00

CD133 epitope vaccine with gp96 as adjuvant elicits an antitumor T cell response against leukemia
Shuo Wang,Hongxia Fan,Yang Li,Huaguo Zheng,Xin Li,Changfei Li,Lizhao Chen,Ying Ju and Songdong Meng.CD133 epitope vaccine with gp96 as adjuvant elicits an antitumor T cell response against leukemia[J].Chinese Journal of Biotechnology,2017,33(6):1006-1017.
Authors:Shuo Wang  Hongxia Fan  Yang Li  Huaguo Zheng  Xin Li  Changfei Li  Lizhao Chen  Ying Ju and Songdong Meng
Institution:1 College of Life Sciences, Hebei University, Baoding 071002, Hebei, China,2 School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China,3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China,3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China,3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China,3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China,3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China,3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China and 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; 4 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
Abstract:Cancer stem cells are currently under intensive investigation due to their capabilities for tumor initiation, self-renewal, and resistance to chemotherapy. CD133 is implicated in stemness and the malignancy of tumor cells. Here, we explored heat shock protein gp96 adjuvanted CD133 epitope vaccine against leukemia. We screened and identified three H2-Kd-restricted cytotoxic T lymphocyte (CTL) epitopes derived from CD133, CD133419-428, CD133702-710 and CD133760-769. The immunogenicity and antitumor activity of the epitope vaccine using heat shock protein gp96 as adjuvant were further determined in CD133+ leukemia xenograft mice. Finally, we demonstrate that adoptive transfer of epitope-specific CTLs led to suppression of leukemia growth. Our data therefore provide the basis for designing a CD133 epitope vaccine to activate specific CTLs against CD133+ leukemia and other cancers.
Keywords:CD133  epitope  gp96  leukemia  CTL
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