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（英文）  

CD133 epitope vaccine with gp96 as adjuvant elicits an antitumor T cell response against leukemia

作　　者：王硕[1] 范红霞[2] 李杨[3] 郑华国 李鑫[3] 李长菲[3] 陈立钊[3] 鞠莹[3] 孟颂东[3,4] 

机构地区：[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 [4]中国科学院大学生命科学学院,北京100049

出　　处：《生物工程学报》2017年第6期1006-1017,共12页Chinese Journal of Biotechnology

基　　金：National Basic Research Program of China(973 Program)(No.2014CB542602);National Natural Science Foundation of China(Nos.31230026,81321063,81471960,81402840,81672815)~~

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-K^d限制性的细胞毒性T细胞(CTL)的表位,分别是CD133_(419–428)、CD133_(702–710)和CD133_(760–769)。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。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.

关 键 词：CD133 表位 GP96 白血病 细胞毒性T细胞 

分 类 号：R733.7[医药卫生—肿瘤]