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1
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.
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
Enhancement of Sindbis virus self-replicating RNA vaccine potency by linkage of Mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene.通过将结核分枝杆菌热休克蛋白70基因与抗原基因连接来增强辛德毕斯病毒自我复制RNA疫苗的效力。
J Immunol. 2001 May 15;166(10):6218-26. doi: 10.4049/jimmunol.166.10.6218.
4
Long-term protection against human papillomavirus e7-positive tumor by a single vaccination of adeno-associated virus vectors encoding a fusion protein of inactivated e7 of human papillomavirus 16/18 and heat shock protein 70.腺相关病毒载体编码 HPV16/18 型 E7 蛋白与热休克蛋白 70 的融合蛋白单次免疫对 HPV 阳性肿瘤的长期保护作用。
Hum Gene Ther. 2010 Jan;21(1):109-19. doi: 10.1089/hum.2009.139.
5
Immunotherapy of a human papillomavirus (HPV) type 16 E7-expressing tumour by administration of fusion protein comprising Mycobacterium bovis bacille Calmette-Guérin (BCG) hsp65 and HPV16 E7.通过给予包含牛分枝杆菌卡介苗(BCG)热休克蛋白65(hsp65)和人乳头瘤病毒16型(HPV16)E7的融合蛋白对表达HPV16 E7的肿瘤进行免疫治疗。
Clin Exp Immunol. 2000 Aug;121(2):216-25. doi: 10.1046/j.1365-2249.2000.01293.x.
6
Low-dose adenovirus vaccine encoding chimeric hepatitis B virus surface antigen-human papillomavirus type 16 E7 proteins induces enhanced E7-specific antibody and cytotoxic T-cell responses.编码嵌合型乙型肝炎病毒表面抗原-16型人乳头瘤病毒E7蛋白的低剂量腺病毒疫苗可诱导增强的E7特异性抗体和细胞毒性T细胞反应。
J Virol. 2005 Oct;79(20):12807-17. doi: 10.1128/JVI.79.20.12807-12817.2005.
7
Human papillomavirus type 16 E7 DNA vaccine: mutation in the open reading frame of E7 enhances specific cytotoxic T-lymphocyte induction and antitumor activity.人乳头瘤病毒16型E7 DNA疫苗:E7开放阅读框中的突变增强特异性细胞毒性T淋巴细胞诱导及抗肿瘤活性。
J Virol. 1999 Sep;73(9):7877-81. doi: 10.1128/JVI.73.9.7877-7881.1999.
8
Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides.接种长肽疫苗后,已建立的表达人乳头瘤病毒16型的肿瘤可被有效根除。
J Immunol. 2002 Jul 1;169(1):350-8. doi: 10.4049/jimmunol.169.1.350.
9
Generation of anti-tumor immunity using mammalian heat shock protein 70 DNA vaccines for cancer immunotherapy.利用哺乳动物热休克蛋白70 DNA疫苗产生抗肿瘤免疫用于癌症免疫治疗。
Vaccine. 2006 Jun 19;24(25):5360-70. doi: 10.1016/j.vaccine.2006.04.028. Epub 2006 May 2.
10
An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response.一种经过改进的重排人乳头瘤病毒16型E7 DNA候选疫苗(HPV-16 E7SH)可诱导E7野生型特异性T细胞应答。
Vaccine. 2006 Apr 5;24(15):2880-93. doi: 10.1016/j.vaccine.2005.12.061. Epub 2006 Jan 19.

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Teaching an old vector new tricks: the surprising versatility of AAV vaccines.教老载体新把戏:腺相关病毒疫苗出人意料的多功能性
J Virol. 2025 Aug 19;99(8):e0073025. doi: 10.1128/jvi.00730-25. Epub 2025 Jul 14.
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Preclinical Immunogenicity and Efficacy Studies for Therapeutic Vaccines for Human Papillomavirus-Type-16-Associated Cancer.人乳头瘤病毒16型相关癌症治疗性疫苗的临床前免疫原性和疗效研究
Vaccines (Basel). 2024 Jun 4;12(6):616. doi: 10.3390/vaccines12060616.
3
Nanotechnology in cervical cancer immunotherapy: Therapeutic vaccines and adoptive cell therapy.纳米技术在宫颈癌免疫治疗中的应用:治疗性疫苗与过继性细胞疗法
Front Pharmacol. 2022 Dec 16;13:1065793. doi: 10.3389/fphar.2022.1065793. eCollection 2022.
4
Prophylactic and Therapeutic HPV Vaccines: Current Scenario and Perspectives.预防性和治疗性 HPV 疫苗:现状与展望。
Front Cell Infect Microbiol. 2022 Jul 4;12:909223. doi: 10.3389/fcimb.2022.909223. eCollection 2022.
5
Cervical Cancer Immunotherapy: Facts and Hopes.宫颈癌免疫治疗:现状与展望。
Clin Cancer Res. 2021 Sep 15;27(18):4953-4973. doi: 10.1158/1078-0432.CCR-20-2833. Epub 2021 Apr 22.
6
A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins.一种用于鉴定 HPV16、18、31 和 45 致癌蛋白中治疗性表位的综合计算分析。
PLoS One. 2018 Oct 24;13(10):e0205933. doi: 10.1371/journal.pone.0205933. eCollection 2018.
7
Characterization of HPV18 E6-specific T cell responses and establishment of HPV18 E6-expressing tumor model.人乳头瘤病毒18型E6特异性T细胞反应的特征分析及人乳头瘤病毒18型E6表达肿瘤模型的建立。
Vaccine. 2017 Jul 5;35(31):3850-3858. doi: 10.1016/j.vaccine.2017.05.081. Epub 2017 Jun 7.
8
The current state of therapeutic and T cell-based vaccines against human papillomaviruses.针对人乳头瘤病毒的治疗性疫苗和基于T细胞的疫苗的当前状况。
Virus Res. 2017 Mar 2;231:148-165. doi: 10.1016/j.virusres.2016.12.002. Epub 2016 Dec 6.
9
Perspectives for therapeutic HPV vaccine development.治疗性人乳头瘤病毒疫苗的研发前景。
J Biomed Sci. 2016 Nov 4;23(1):75. doi: 10.1186/s12929-016-0293-9.
10
Current state in the development of candidate therapeutic HPV vaccines.候选治疗性人乳头瘤病毒疫苗的研发现状
Expert Rev Vaccines. 2016 Aug;15(8):989-1007. doi: 10.1586/14760584.2016.1157477. Epub 2016 Mar 7.

本文引用的文献

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Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: induction of cytotoxic T cells and specific tumor protection.对人乳头瘤病毒16型L1E7嵌合病毒样颗粒的免疫反应:细胞毒性T细胞的诱导及特异性肿瘤保护作用
Int J Cancer. 1999 Jun 11;81(6):881-8. doi: 10.1002/(sici)1097-0215(19990611)81:6<881::aid-ijc8>3.0.co;2-t.
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rAAV vector-mediated sarcogylcan gene transfer in a hamster model for limb girdle muscular dystrophy.rAAV载体介导的肌聚糖基因转移在肢带型肌营养不良仓鼠模型中的应用
Gene Ther. 1999 Jan;6(1):74-82. doi: 10.1038/sj.gt.3300830.
3
Disease-inducible transgene expression from a recombinant adeno-associated virus vector in a rat arthritis model.重组腺相关病毒载体在大鼠关节炎模型中诱导疾病的转基因表达。
J Virol. 1999 Apr;73(4):3410-7. doi: 10.1128/JVI.73.4.3410-3417.1999.
4
Mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in mice.用乳头瘤病毒样颗粒进行黏膜免疫可在小鼠体内引发全身免疫和黏膜免疫。
Virology. 1998 Dec 5;252(1):39-45. doi: 10.1006/viro.1998.9442.
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Experimental vaccine strategies for cancer immunotherapy.癌症免疫治疗的实验性疫苗策略。
J Biomed Sci. 1998 Jul-Aug;5(4):231-52. doi: 10.1007/BF02255855.
6
Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus.在无辅助腺病毒情况下生产高滴度重组腺相关病毒载体。
J Virol. 1998 Mar;72(3):2224-32. doi: 10.1128/JVI.72.3.2224-2232.1998.
7
Immunization with human papillomavirus type 16 (HPV16) oncoprotein-loaded dendritic cells as well as protein in adjuvant induces MHC class I-restricted protection to HPV16-induced tumor cells.用人乳头瘤病毒16型(HPV16)癌蛋白负载的树突状细胞以及佐剂中的蛋白进行免疫接种,可诱导对HPV16诱导的肿瘤细胞的MHC I类限制性保护。
Cancer Res. 1998 Feb 15;58(4):724-31.
8
Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model.嵌合乳头瘤病毒样颗粒在HPV16肿瘤模型中引发针对E7癌蛋白的抗肿瘤免疫。
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1800-5. doi: 10.1073/pnas.95.4.1800.
9
Heat shock fusion proteins as vehicles for antigen delivery into the major histocompatibility complex class I presentation pathway.热休克融合蛋白作为抗原递送至主要组织相容性复合体I类呈递途径的载体。
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13146-51. doi: 10.1073/pnas.94.24.13146.
10
Genetically modified bone marrow-derived dendritic cells expressing tumor-associated viral or "self" antigens induce antitumor immunity in vivo.表达肿瘤相关病毒或“自身”抗原的基因改造骨髓源性树突状细胞可在体内诱导抗肿瘤免疫。
Eur J Immunol. 1997 Oct;27(10):2702-7. doi: 10.1002/eji.1830271033.

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。

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.

作者信息

Liu D W, Tsao Y P, Kung J T, Ding Y A, Sytwu H K, Xiao X, Chen S L

机构信息

Department of Microbiology and Immunology, Taipei, Taiwan, Republic of China.

出版信息

J Virol. 2000 Mar;74(6):2888-94. doi: 10.1128/jvi.74.6.2888-2894.2000.

DOI:10.1128/jvi.74.6.2888-2894.2000
PMID:10684306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC111780/
Abstract

In this study, we explore a potential vaccine for human papillomavirus (HPV)-induced tumors, using heat shock protein as an adjuvant, a peptide vaccine for safety, and adeno-associated virus (AAV) as a gene delivery vector. The tumor vaccine was devised by constructing a chimeric gene which contained HPV type 16 E7 cytotoxic T-lymphocyte (CTL) epitope DNA (M. C. Feltkamp, H. L. Smits, M. P. Vierboom, R. P. Minnaar, B. M. de Jongh, J. W. Drijfhout, J. ter Schegget, C. J. Melief, and W. M. Kast, Eur. J. Immunol. 23:2242-2249, 1993) fused with the heat shock protein gene as a tumor vaccine delivered via AAV. Our results demonstrate that this vaccine can eliminate tumor cells in syngeneic animals and induce CD4- and CD8-dependent CTL activity in vitro. Moreover, studies with knockout mice with distinct T-cell deficiencies confirm that CTL-induced tumor protection is CD4 and CD8 dependent. Taken together, the evidence indicates that this chimeric gene delivered by AAV has potential as a cervical cancer vaccine.

摘要

在本研究中,我们探索了一种用于人乳头瘤病毒(HPV)诱导肿瘤的潜在疫苗,使用热休克蛋白作为佐剂,一种安全的肽疫苗,并以腺相关病毒(AAV)作为基因递送载体。通过构建一个嵌合基因来设计肿瘤疫苗,该嵌合基因包含人乳头瘤病毒16型E7细胞毒性T淋巴细胞(CTL)表位DNA(M.C.费尔特坎普、H.L.斯米茨、M.P.维博姆、R.P.明纳尔、B.M.德容、J.W.德里福特、J.特谢格特、C.J.梅利夫和W.M.卡斯特,《欧洲免疫学杂志》23:2242 - 2249,1993年),并与热休克蛋白基因融合,作为通过AAV递送的肿瘤疫苗。我们的结果表明,这种疫苗能够消除同基因动物体内的肿瘤细胞,并在体外诱导依赖CD4和CD8的CTL活性。此外,对具有不同T细胞缺陷的基因敲除小鼠的研究证实,CTL诱导的肿瘤保护作用依赖于CD4和CD8。综上所述,证据表明由AAV递送的这种嵌合基因有潜力成为一种宫颈癌疫苗。