用于宫颈癌免疫治疗的表达人乳头瘤病毒蛋白的重组痘苗病毒的构建与特性分析
Construction and characterisation of a recombinant vaccinia virus expressing human papillomavirus proteins for immunotherapy of cervical cancer.
作者信息
Boursnell M E, Rutherford E, Hickling J K, Rollinson E A, Munro A J, Rolley N, McLean C S, Borysiewicz L K, Vousden K, Inglis S C
机构信息
Cantab Pharmaceuticals Research Ltd., Cambridge, UK.
出版信息
Vaccine. 1996 Nov;14(16):1485-94. doi: 10.1016/s0264-410x(96)00117-x.
Abstract
The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modified forms of the E6 and E7 proteins from HPV16 and HPV18, the viruses most commonly associated with cervical cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine strain of vaccinia, and was shown to express the desired gene products. Studies in mice indicated that the recombinant virus was less neurovirulent than the parental virus and was capable of inducing an HPV-specific CTL response. This pre-clinical evaluation has provided a basis for the initiation of human trials in cervical cancer patients.
摘要
在绝大多数宫颈肿瘤中，编码人乳头瘤病毒（HPV）E6和E7蛋白的基因的存在及持续表达为通过免疫治疗方法控制该疾病提供了契机。本报告描述了一种重组痘苗病毒的构建及特性，该病毒旨在表达来自HPV16和HPV18的E6和E7蛋白的修饰形式，这两种病毒是最常与宫颈癌相关的病毒。重组病毒（命名为TA-HPV）基于惠氏痘苗疫苗株，且已证明其能表达所需的基因产物。对小鼠的研究表明，重组病毒的神经毒性低于亲本病毒，并且能够诱导HPV特异性CTL反应。这种临床前评估为启动针对宫颈癌患者的人体试验提供了依据。
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Reversible repression of papillomavirus oncogene expression in cervical carcinoma cells: consequences for the phenotype and E6-p53 and E7-pRB interactions.人乳头瘤病毒癌基因表达在宫颈癌细胞中的可逆性抑制：对细胞表型及E6-p53和E7-pRB相互作用的影响
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