IMMUNOLOGY OF VIRUS INDUCED PAPILLOMAS/CARCINOMAS

病毒引起的乳头状瘤/癌的免疫学

• 批准号: 3194749
• 负责人: FELIX O WETTSTEIN
• 金额: $ 27.14万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3194749
• 关键词: B lymphocyte; Shope papilloma; T lymphocyte; antibody; cell transformation; cellular immunity; chimeric proteins; cutaneous papilloma; cytotoxic T lymphocyte; genetic manipulation; human papillomavirus; interleukin 2; laboratory rabbit; leukocyte activation /transformation; neoplasm /cancer therapy; protein engineering; rabbit papillomavirus; simian virus 40; vaccinia virus; viral vaccines; virus protein; western blottings

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.

宫颈癌是世界范围内女性最常见的癌症之一。 大多数（如果不是全部）含有人乳头瘤病毒（HPV）DNA，HPV 目前的HPV类型是与良性或恶性肿瘤相关的HPV类型的亚组， 生殖器癌前病变 癌症是从癌前病变 癌症相关亚组的病变。 在癌症中， 在癌症衍生的细胞系中，病毒DNA继续转录， 编码两种早期蛋白质E6和E7 棉尾兔 乳头状瘤病毒（CRPV）及其诱导的肿瘤提供了一种动物 模型来研究宿主、病毒和进化中的 肿瘤 CRPV诱导角化中的良性肿瘤（乳头状瘤） 家兔和棉尾兔（自然宿主）的上皮。 乳头状瘤可自发消退或持续存在并进展为侵袭性 和高频率的转移性癌症，特别是在家庭中， 家兔 如在人类癌症中，E6和E7蛋白的mRNA是 在兔子的癌症中含量最高 我们的长期目标是从广义上阐明各种宿主 兔子系统中的互动 具体目标是： 1. 免疫状态的表征 a. 在乳头状瘤的发展过程中。 B. 在自然消退过程中。 C. 在癌症的发展过程中。 通过：i）分析血清中的非结构性病毒抗体 proteins. ii）检查CRPV特异性细胞毒性T细胞淋巴细胞 (CTL)并绘制这些细胞识别的病毒表位。 （三） 测定淋巴增殖性（T细胞）对病毒的应答 肽或蛋白质，从病毒或致癌物质（DMBA）提取物 诱导的乳头状瘤或表达病毒蛋白的细胞。 （四）计量 迟发型超敏反应 2. 乳头状瘤和癌细胞的特征 病毒和辅助蛋白（MHC和ICAM）的表达需要 免疫识别的能力。 3. 免疫反应的改变 a. 病毒或病毒DNA攻毒前 B. 在乳头状瘤的发展过程中。 C. 在进展为癌后。 通过; i）用表达以下的重组牛痘病毒免疫： 非结构或结构CRPV蛋白。 （二）免疫接种 由病毒或DMBA诱导的肿瘤制备的疫苗。 （三） 细胞因子的施用。