IMMUNOLOGY OF VIRUS INDUCED PAPILLOMAS/CARCINOMAS

病毒引起的乳头状瘤/癌的免疫学

基本信息

批准号：
2093716
负责人：
FELIX O WETTSTEIN
金额：
$ 29.35万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-01 至 1995-04-30
项目状态：
已结题

项目摘要

Cervical cancer is one of the most common cancers in women world-wide. Most, if not all, contain human papillomavirus (HPV) DNA and the HPV types present are a subgroup of HPV types associated with benign or premalignant genital lesions. The cancers evolve from premalignant lesions of the cancer associated subgroup. In cancer, as well as in cancer derived cell lines, viral DNA continues to be transcribed which encodes the two early proteins, E6 and E7. The cottontail rabbit papillomavirus (CRPV) and the neoplasias induced by it provide an animal model to study the interactions between host, virus and the evolving neoplasias. CRPV induces benign tumors (papillomas) in the keratinizing epithelium of domestic and cottontail rabbits (the natural host). Papillomas may regress spontaneously or persist and progress to invasive and metastasizing cancers at a high frequency, particularly, in domestic rabbits. As in the human cancers, mRNA for the E6 and E7 proteins are the most abundant in rabbit cancers. Our long-term goal is to elucidate in a broad sense various host interaction in the rabbit system. The specific aims are: 1. Characterization of the immune status a. During papilloma development. b. During spontaneous regression. c. During development of cancers. By; i) The analysis of serum for antibodies to nonstructural viral proteins. ii) Checking for CRPV specific cytotoxic T cell lymphocytes (CTL) and mapping viral epitopes recognized by these cells. iii) Determination of the lymphoproliferative (T cell) response to viral peptides or proteins, to extracts from virus or carcinogen (DMBA) induced papillomas or to cells expressing viral proteins. iv) Measuring delayed type hypersensitivity. 2. Characterization of papilloma and carcinoma cells with respect to the expression of viral and auxiliary proteins (MHC and ICAM) required for immune recognition. 3. Modification of the immune response a. Before challenge with virus or viral DNA b. During papilloma development. c. After progression to carcinomas. By; i) Immunization with recombinant vaccinia virus expressing nonstructural or structural CRPV proteins. ii) Immunization with vaccines prepared from virus or DMBA induced tumors. iii) Administration of cytokines.

宫颈癌是全球女性最常见的癌症之一。大多数（如果不是全部）包含人乳头瘤病毒（HPV）DNA和HPV 存在的类型是与良性相关的HPV类型的子组预先陈列的生殖器病变。癌症是从预先出现的癌症相关亚组的病变。在癌症中以及癌症衍生的细胞系，病毒DNA继续被转录编码两个早期蛋白E6和E7。棉尾兔乳头瘤病毒（CRPV）和由其诱导的肿瘤提供了动物研究宿主，病毒与不断发展的宿主相互作用的模型肿瘤。 CRPV在角化化中诱导良性肿瘤（乳头状瘤）家庭和棉尾兔（天然宿主）上皮。乳头状瘤可能会自发地退回或持久退回并进展为侵入性并以高频转移癌症，特别是在国内兔子。与人类癌一样，E6和E7蛋白的mRNA是兔子癌中最丰富。我们的长期目标是在广义上阐明各种主机兔子系统中的相互作用。具体目的是： 1。免疫状态的表征一个。在乳头状瘤发展期间。 b。在自发回归期间。 c。在癌症的发展过程中。经过; i）分析非结构病毒抗体的血清蛋白质。 ii）检查CRPV特异性细胞毒性T细胞淋巴细胞这些细胞识别的（CTL）和映射病毒表位。 iii）测定淋巴增生性（T细胞）对病毒的反应肽或蛋白质，从病毒或致癌物（DMBA）提取诱导乳头瘤或表达病毒蛋白的细胞。 iv）测量延迟类型的超敏反应。 2。相对于乳头状瘤和癌细胞的表征需要病毒和辅助蛋白（MHC和ICAM）的表达用于免疫识别。 3。免疫反应的修改一个。在挑战病毒或病毒DNA之前 b。在乳头状瘤发展期间。 c。进展为癌后。经过; i）用表达重组的牛ac病毒免疫非结构或结构CRPV蛋白。 ii）免疫由病毒或DMBA诱导的肿瘤制备的疫苗。 iii）细胞因子给药。