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用表达人乳头瘤病毒16型E7的重组单核细胞增生李斯特菌进行口服疫苗接种可使小鼠肿瘤消退。

Oral vaccination with recombinant Listeria monocytogenes expressing human papillomavirus type 16 E7 can cause tumor growth in mice to regress.

作者信息

Lin Chih-Wei, Lee Jen-Yi, Tsao Yeou-Ping, Shen Che-Piao, Lai Hung-Cheng, Chen Show-Li

机构信息

Department of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.

出版信息

Int J Cancer. 2002 Dec 20;102(6):629-37. doi: 10.1002/ijc.10759.

Abstract

Listeria monocytogenes is a Gram-positive, facultative intracellular bacterium with the ability to present secreted proteins to the major histocompatibility complex class I pathway to stimulate cell-mediated immune response. In our study, we constructed the recombinant L. monocytogenes encoding human papillomavirus type 16 E7 gene (rLM-E7). When orally administered to syngeneic mice, rLM-E7 could induce a cytotoxic T-lymphocyte (CTL) response. Furthermore, in vitro flow cytometric assay and in vivo immune deficiency assays showed that rLM-E7 could prevent and eradicate tumor growth via CD8+-dependent CTLs. Hence, the potency of rLM-E7 as a therapeutic vaccine for cervical cancer is the result of the induction E7-specific cell-mediated immunity by L. monocytogenes. In addition to potency, this vaccine also offers ease of administration and reduced cost of production compared with other vaccines formulated for injection. Thus, L. monocytogenes encoding HPV-16 E7 may be a useful oral vaccine for cervical cancer treatment.

摘要

单核细胞增生李斯特菌是一种革兰氏阳性兼性胞内细菌,能够将分泌蛋白呈递给主要组织相容性复合体I类途径,以刺激细胞介导的免疫反应。在我们的研究中,我们构建了编码人乳头瘤病毒16型E7基因的重组单核细胞增生李斯特菌(rLM-E7)。当给同基因小鼠口服时,rLM-E7可诱导细胞毒性T淋巴细胞(CTL)反应。此外,体外流式细胞术检测和体内免疫缺陷检测表明,rLM-E7可通过CD8 + 依赖性CTL预防和根除肿瘤生长。因此,rLM-E7作为宫颈癌治疗性疫苗的效力是单核细胞增生李斯特菌诱导E7特异性细胞介导免疫的结果。除了效力之外,与其他注射用疫苗相比,这种疫苗还具有易于给药和生产成本降低的优点。因此,编码HPV-16 E7的单核细胞增生李斯特菌可能是一种用于宫颈癌治疗的有用口服疫苗。

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