MEASUREMENT OF CTL RESPONSES TO HUMAN PAPILLOMA VIRUS

CTL 对人乳头瘤病毒反应的测定

• 批准号: 6844726
• 负责人: Karen Sue Anderson
• 金额: $ 6.34万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-04 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844726
• 关键词: MHC class I antigen; cervix neoplasms; clinical research; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; female; human papillomavirus; human subject; microorganism immunology; neoplastic process; virus antigen; virus diseases; virus protein; women' s health

DESCRIPTION (Applicant's Description): Human papillomavirus (HPV) represents a unique tumor antigen system to determine whether a cell-mediated immune response can directly alter the development of cancer. DNA from human papillomaviruses (HPV) can be found in most cervical carcinomas, and the HPV E6 and E7 gene products are implicated in cervical carcinogenesis through their interaction with p53 and Rb. An intact cell-mediated immune system is thought to be critical for control of HPV infection, since 1) the vast majority of infected HPV+ patients will spontaneously clear their infection, 2 ) the development of cervical neoplasia is HLA-linked, and 3)immunodeficiency, such as HIV infection, alters the progression of HPV infection. There are several ongoing clinical trials [involving] vaccination with HPV E6 and E7-derived antigens, but many questions regarding the endogenous iLnmune response to remain to be addressed. Hypothesis: Infection of patients with human papillomavirus (HPV) subtype 16 triggers a measurable endogenous CD8+ cytotoxic T lymphocyte (CTL) response to HPV-derived peptides, and the failure to develop functional anti-HPV CTL correlates with persistence of infection and progression to cervical neoplasia. To address this hypothesis, Dr. Anderson plans to accomplish the following aims: 1) Using a combination of tetramer and ELISpot assays, determine whether normal HLA-A2+ blood donors have measurable and functional HPV16 E6 and E7-specific CTL, and whether these CTL can be expanded in vitro. 2) Determine if HPV16-infected patients mount an anti-HPV CTL response that inversely correlates with progression of cervical neoplasia. This will be done by enumerating, expanding, and phenotyping CTL from HPV16+ patients who have a range of cervical abnormalities, from normal cytology to cervical carcinoma. Dr. Anderson's research will be performed in a laboratory at the Dana-Farber Cancer Institute under the sponsorship of Dr. Lee M, Nadler, a leader in the f i eld of tumor immunology and experienced mentor of many successful physician/scientists.

描述（申请人描述）：人乳头瘤病毒（HPV）代表 一个独特的肿瘤抗原系统，以确定是否有细胞介导的免疫反应， 反应可以直接改变癌症的发展。 人类DNA 乳头瘤病毒（HPV）可以在大多数宫颈癌中发现，并且HPV E6和E7基因产物与宫颈癌的发生有关， 它们与p53和Rb的相互作用。 一个完整的细胞介导的免疫系统是 被认为是控制HPV感染的关键，因为1） 大多数感染HPV+的患者将自发清除其感染， （二） 的 发展 的 宫颈 瘤变 是 HLA连锁， 和 3）免疫缺陷，如HIV感染，改变HPV的进展 感染 有几个正在进行的临床试验[涉及]疫苗接种 与HPV E6和E7衍生抗原，但许多问题， 内源性免疫应答仍有待解决。 假设：感染 的人乳头瘤病毒（HPV）亚型16患者触发了可测量的 内源性CD 8+细胞毒性T淋巴细胞（CTL）对HPV衍生肽的应答， 不能产生功能性抗HPV CTL与持续性 感染和发展为宫颈肿瘤。 为了解决这个 安德森博士计划实现以下目标：1）使用 四聚体和ELISpot测定的组合，确定正常HLA-A2+ 献血者具有可测量和功能性HPV 16 E6和E7特异性CTL， 这些CTL是否可以在体外扩增。 2)确定是否感染HPV 16 患者产生抗HPV CTL应答， 进展 子宫颈肿瘤 这将通过枚举来完成， 扩增来自HPV 16+患者的CTL并对其进行表型分型， 宫颈异常，从正常细胞学到宫颈癌。 博士 安德森的研究将在达纳法伯大学的实验室进行 癌症研究所的赞助下，博士李M，纳德勒，在领导者， 肿瘤免疫学领域的专家和许多成功的 医生/科学家