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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.

DOI:10.1002/ijc.10759
PMID:12448006
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。

相似文献

1
Oral vaccination with recombinant Listeria monocytogenes expressing human papillomavirus type 16 E7 can cause tumor growth in mice to regress.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。
Int J Cancer. 2002 Dec 20;102(6):629-37. doi: 10.1002/ijc.10759.
2
Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16.两种表达人乳头瘤病毒16型(HPV - 16)E7不同分子形式的单核细胞增生李斯特菌疫苗载体诱导出性质不同的T细胞免疫,这与其诱导由HPV - 16永生化的已建立肿瘤消退的能力相关。
J Immunol. 2001 Dec 1;167(11):6471-9. doi: 10.4049/jimmunol.167.11.6471.
3
Recombinant Listeria vaccines containing PEST sequences are potent immune adjuvants for the tumor-associated antigen human papillomavirus-16 E7.含有PEST序列的重组李斯特菌疫苗是针对肿瘤相关抗原人乳头瘤病毒16 E7的强效免疫佐剂。
Cancer Res. 2004 Dec 15;64(24):8821-5. doi: 10.1158/0008-5472.CAN-04-1958.
4
Prophylactic and therapeutic efficacy of an attenuated Listeria monocytogenes-based vaccine delivering HPV16 E7 in a mouse model.基于减毒李斯特菌的 HPV16 E7 疫苗在小鼠模型中的预防和治疗效果。
Int J Mol Med. 2012 Dec;30(6):1335-42. doi: 10.3892/ijmm.2012.1136. Epub 2012 Sep 20.
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A Genetically Modified attenuated Vaccine Expressing HPV16 E7 Kill Tumor Cells in Direct and Antigen-Specific Manner.一种表达人乳头瘤病毒16型E7蛋白的基因工程减毒疫苗以直接和抗原特异性方式杀伤肿瘤细胞。
Front Cell Infect Microbiol. 2017 Jun 29;7:279. doi: 10.3389/fcimb.2017.00279. eCollection 2017.
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Regression of HPV-positive tumors treated with a new Listeria monocytogenes vaccine.用新型单核细胞增生李斯特菌疫苗治疗的HPV阳性肿瘤的消退
Arch Otolaryngol Head Neck Surg. 2004 Jan;130(1):92-7. doi: 10.1001/archotol.130.1.92.
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Recombinant adeno-associated virus expressing human papillomavirus type 16 E7 peptide DNA fused with heat shock protein DNA as a potential vaccine for cervical cancer.表达与人乳头瘤病毒16型E7肽DNA融合的热休克蛋白DNA的重组腺相关病毒作为宫颈癌的潜在疫苗。
J Virol. 2000 Mar;74(6):2888-94. doi: 10.1128/jvi.74.6.2888-2894.2000.
8
Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors.将人乳头瘤病毒16型E7靶向内体/溶酶体区室可增强DNA疫苗对表达人乳头瘤病毒16型E7的小鼠肿瘤的抗肿瘤免疫力。
Hum Gene Ther. 1999 Nov 20;10(17):2727-40. doi: 10.1089/10430349950016474.
9
Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine.人乳头瘤病毒16型E6和E7长肽疫苗诱导宫颈癌患者肿瘤特异性CD4+和CD8+ T细胞免疫
Clin Cancer Res. 2008 Jan 1;14(1):178-87. doi: 10.1158/1078-0432.CCR-07-1880.
10
Both E7 and CpG-oligodeoxynucleotide are required for protective immunity against challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells: involvement of CD4+ and CD8+ T cells in protection.E7和CpG-寡脱氧核苷酸对于抵抗人乳头瘤病毒16型(E6/E7)永生化肿瘤细胞攻击的保护性免疫均是必需的:CD4+和CD8+ T细胞参与保护作用。
Cancer Res. 2002 Dec 15;62(24):7234-40.

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