由美国森瑞生命科学研究所研制、中国森瑞谱生产、雅帆国际全权代理的蕊美人清除高危型HPV病毒产品技术再次受邀出席第33届国际HPV大会，本届大会在西班牙巴塞罗那举行，蕊美人清除高危型HPV病毒技术再一次登上国际舞台，被来自世界各地的HPV学术专家认可。

国际HPV大会(国际人乳头瘤病毒学会)International human Papilloma virus Society，总部设立在中国香港，是一个公益性国际学术组织，旨在调查和研究全球人乳头瘤(HPV)病毒及其相关疾病领域的生物医学科学家的不以营利为目的的国际组织，是国际性学术团体，是发展全球医学科学技术和研究、预防人乳头瘤(HPV)病毒医学事业的重要国际力量。

蕊美人清除HPV病毒感染的产品技术，早在2010年起就受到国际HPV大会的邀请，其中在2011年德国柏林召开的《第27届HPV国际学术会议》上，蕊美人清除HPV病毒感染的产品技术还被作为唯一的清除高危HPV病毒感染产品在大会上做学术报告，，是被“HPV国际学术会议”首肯的有效清除HPV病毒感染的突破性创新产品。

然而今年，蕊美人清除HPV病毒感染的产品技术再次连续受到国际HPV大会主办方的邀请，那么在本届国际HPV大会上又发表了哪些新的学术报告呢?跟随蕊美人一起来看看吧!

蕊美人了解到在第33届国际HPV大会的第二天，大会发表了《Development of Spontaneous Hpv-16 E6/E7-Expressing Cervicovaginal Preclinical Model that Follows Clinical Tumor Progression Via Integration of HPV Oncogenes (ID 277)》自然表达HPV-16 E6/E7的子宫颈阴道临床前模型的建立，通过HPV致癌基因整合来跟踪临床肿瘤进展的报告，以下为报告内容：

TALIA R. HENKLE (United States of America)

Introduction

A suitable preclinical HPV tumor model should possess the following characteristics:(1)forms spontaneous, localized, HPV-16 E6/E7-expressing tumor,(2)displays carcinoma morphology,(3)possesses locally immunosuppressive tumor microenvironment, resembling that of HPV16(+) tumors in patients,(4)tumor formation follows clinical progression starting from precancerous to cancerous state,(5)tumor- bearing mice can respond appropriately to immunotherapeutic strategies and generate antitumor immunity, and (6)tumorigenesis can be easily monitored.

Methods

To this end, we recently developed a method to induce the spontaneous formation of HPV-16 E6/E7-expressing tumors in the cervicovaginal tracts of C57BL/6 mice by transiently depleting systemic T cells and submucosally injecting plasmids encoding HPV16 E6/E7, luciferase, constitutively active AKT,c-Myc, and Sleeping Beauty transposase into the cervicovaginal area of mice,followed by electroporation. Tumor formation was closely monitoried by bioluminescence imaging and gene expressions were characterized by immunohistochemical staining and RNA in situ hybridization.

Results

Formation of luciferase-expressing tumor in the cervicovaginal tract of injected mice occurred in 80-100% of animals by week 5 after electroporation (Figure 1). Remarkably, histologic progression from precancerous lesions (squamous intraepitheliual lesions) to invasive squamous cell carcinoma resembled cancer progression of HPV-associated malignancies in human patients (Figure 2). Furthermore, the expression of transfected oncogenes and HPV E6/E7 oncogenes was demonstrated in the tumor (Figure 3).

Figure 2. Progression of lesion from LSIL>HSIL SCC in spontaneous HPV+ cervicovaginal carcinoma model. At each timepoint corresponding with the indicated luminescence value, 3 mice were sacrificed and their reproductive tract was harvested for sectioning (A) Representative images of vaginal tissue with ~105 luminescence signal at 1 week post-electroporation exhibiting low grade squamous intraepithelial lesion ( LSIL )[see box]. (B) Representative images of vaginal tissue with ~10 luminescence signal at 2 weeks post electroporation exhibiting high grade squamous intraepithelial lesion (HSIL). (C) Representative images of vaginal tissue with ~107 luminescence signal at 3 weeks post -electroporation exhibiting HSIL and invasive carcinoma [see box]. (D) Representative images of tumor tissue with ~108 luminescence signal at 4 weeks post-electroporation. Tumor presents as elldifferentiated SCC with presence of keratin pearls [see box]

Conclusions

This new preclinical tumor model has potential utility for the preclinical evaluation of treatments for precancerous lesions, and offers several advantages as preclinical model for HPV-associated malignancies for the evaluation of novel cancer treatments and immunotherapies compared to transplantable tumor models and transgenic mouse models such as the ability to extend to the creation of tumor model generated by different high risk types of HPV, the lack of central immune tolerance for HPV E6/E7 oncogenic proteins and the application to mice with different MHC class genetic background.

简介

一个合适的临床前HPV肿瘤模型应具有以下特点: (1)形成自然的、局部的、表达HPV-16E6/E7的肿瘤;(2)显示肿瘤的形态;(3)具有类似HPV16(+)肿瘤患者那样的局部免疫抑制的肿瘤微环境;(4)肿瘤的形成遵循从癌前病变到癌变的临床进程;(5)荷瘤小鼠能够对免疫治疗策略做出适当的反应并产生抗肿瘤免疫; (6)肿 瘤的发生过程易于监测。

方法

为此，我们最近开发了一种方法，通过在小鼠子宫颈阴道部位瞬时耗尽免疫系统T细胞和黏膜下注射编码HPV16 E6/E7、荧光素酶、激活型AKT、c-Myc、 睡美人转座子的表达质粒，然后进行电穿孔，来诱导C57BL/6小鼠子官颈阴道部位形成自然表达HPV-16 E6/E7肿瘤。生物发光成像密切监控肿瘤的形成，免疫组织化学染色和RNA原位杂交检测基因表达。

结果

在电穿孔后的第5周，有80-100%的注射小鼠在子宫颈阴道部位形成了荧光素酶表达的肿瘤(图1)。 值得注意的是，从癌前病变(鳞状上皮内病变)到鳞状细胞浸润癌的组织学进展与人类乳头状瘤病毒相关恶性肿瘤的进展相似(图2)。此外，肿瘤中显示了转染致癌基因和HPVE6/E7致癌基因的表达(图3)。

结论

这种新的临床前肿瘤模型对于癌前病变治疗的临床前评估具有潜在的实用价值，与可移植肿瘤模型和转基因小鼠模型相比，作为HPV相关恶性肿瘤的临床前模型在评估新的癌症治疗和免疫疗法方面具有以下优势，例如能够扩展到由不同高危类型的HPV生成的肿瘤模型的创建，对HPVE6/E7致癌基因蛋白缺乏中枢免疫耐受性及其在不同MHC类别遗传背景小鼠中的应用。