Rejection of Tumors by MHC Class Ib-Restricted CTL

MHC Ib 类限制性 CTL 对肿瘤的排斥

• 批准号: 6944827
• 负责人: EUGENE Y CHIANG
• 金额: $ 4.83万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6944827
• 关键词: MHC class I antigen; carcinogenesis inhibitor; cell growth regulation; cell line; cell population study; cytotoxic T lymphocyte; cytotoxicity; genetic regulation; genetic transcription; host neoplasm interaction; immunoregulation; intermolecular interaction; laboratory mouse; melanoma; microarray technology; molecular oncology; neoplasm /cancer genetics; neoplastic cell; neoplastic process; postdoctoral investigator; protein structure function; tumor antigens

DESCRIPTION (provided by applicant): Q9, a murine non-polymorphic nonclassical class Ib MHC molecule, has been observed to be downregulated or lost in all Q9-expressing mouse strain-derived tumor cell lines. Furthermore, Q9 has been found to confer protection to host animals from melanoma tumor challenge. The focus of this application is to determine if Q9 functions as a restriction element for syngeneic tumor-reactive CTLs. The proposed experiments aim to establish protocols for the determination of CTL participation in Q9-mediated rejection of model tumors and for the generation of highly potent antitumor CTLs, to provide a detailed characterization of these CTLs, and to evaluate potential tumor-associated antigens that are presented in the context of Q9. Methods used to achieve these aims will include in vitro cytotoxicity assays, flow cytometry analyses, microarray analyses, laser capture microscopy, real-time quantitative PCR and protein purification. These studies may lead to the development of universal peptide vaccines, thereby providing a significant contribution to the treatment of cancers. Work with the Q9 model class Ib antigen will also lay a foundation for future studies with human class I MHC such as HLA-C and/or HLA-E, -F, -G or other yet undiscovered class I molecules.

描述（由申请人提供）：Q9是一种鼠类非多态性非经典Ib类MHC分子，已观察到在所有表达Q9的小鼠品系衍生的肿瘤细胞系中下调或丢失。此外，已发现 Q9 可以保护宿主动物免受黑色素瘤的攻击。本应用的重点是确定 Q9 是否作为同基因肿瘤反应性 CTL 的限制元件发挥作用。拟议的实验旨在建立确定 CTL 参与 Q9 介导的模型肿瘤排斥和生成高效抗肿瘤 CTL 的方案，提供这些 CTL 的详细表征，并评估 Q9 背景下存在的潜在肿瘤相关抗原。用于实现这些目标的方法包括体外细胞毒性测定、流式细胞术分析、微阵列分析、激光捕获显微镜、实时定量PCR和蛋白质纯化。这些研究可能会导致通用肽疫苗的开发，从而为癌症的治疗做出重大贡献。使用 Q9 模型 Ib 抗原也将为未来研究人类 I 类 MHC（例如 HLA-C 和/或 HLA-E、-F、-G 或其他尚未发现的 I 类分子）奠定基础。