T CELL FOCUSED CANCER VACCINES IN MURINE TUMOR MODELS

小鼠肿瘤模型中的 T 细胞癌症疫苗

• 批准号: 6173080
• 负责人: ROBERT K BRIGHT
• 金额: $ 9.87万
• 依托单位: PROVIDENCE PORTLAND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173080
• 关键词: MHC class I antigen; active immunization; astrocytoma; cytotoxic T lymphocyte; disease /disorder model; drug screening /evaluation; ependymoma; immunogenetics; laboratory mouse; mesothelioma; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; neoplastic cell; neoplastic transformation; nonhuman therapy evaluation; osteosarcoma; simian virus 40; synthetic peptide; tumor antigens; virus antigen; virus genetics; virus protein; virus related neoplasm /cancer

DESCRIPTION: (Applicant's Abstract) One in six people will die of cancer. the systemic nature, recall ability and exquisite specificity of the immune system makes immunotherapy an attractive prospect for cancer treatment. Hepatocellular carcinoma, cervical carcinoma, various leukemias and lymphomas all have proposed viral etiologies. Viral encoded tumor specific antigens make viral associated tumors strong candidates for immunotherapy. Recent studies have described the presence of simian virus 40 (SV40)-like gene sequences and proteins (specifically the large tumor antigen: SV40 Tag) in human osteosarcomas, glioblastomas, ependymomas and malignant pleural mesotheliomas (MPM), demonstrating SV40 association with certain human malignancies. To facilitate the development of human clinical protocols for the immunotherapy of SV40 associated human malignancies, the proposed study will employ an SV40 murine tumor system to evaluate the efficacy of CTL transfer therapies and peptide based vaccines designed to target an immune response to SV40 Tag expressing tumors in vivo. Briefly, SV40 Tag specific CTL will be generated by immunization of Balb/c mice with SV40 Tag gene constructs and the epitope specificity determined by using selected H-2d restricted synthetic peptides representing potential CTL epitopes on SV40 Tag. These CTL will be utilized to examine the ability of adoptively transferred T cells to protect against tumor challenge in syngeneic mice. Further, selected synthetic peptides will be examined for the ability to actively induce protective tumor immunity in vivo. Completion of this study will provide valuable information on the active induction of tumor destructive immunity involving SV40 Tag-epitope specific CTL in vivo. Moreover, the information generated using the murine SV40 tumor model will expedite the development of reagents and clinical trials designed to examine SV40 Tag specific immunotherapies for SV40 associated human malignancies.

描述：（申请人摘要）六分之一的人将死于癌症。 免疫的系统性、记忆能力和精确的特异性 系统使免疫疗法成为癌症治疗的一个有吸引力的前景。 肝细胞癌、宫颈癌、各种白血病等 淋巴瘤均已提出病毒病因。 病毒编码的肿瘤特异性 抗原使病毒相关肿瘤成为免疫治疗的有力候选者。 最近的研究描述了类猿猴病毒 40 (SV40) 的存在 基因序列和蛋白质（特别是大肿瘤抗原：SV40 标签）在人类骨肉瘤、胶质母细胞瘤、室管膜瘤和恶性 胸膜间皮瘤 (MPM)，证明 SV40 与某些 人类恶性肿瘤。 促进人类临床的发展 SV40 相关人类恶性肿瘤的免疫治疗方案 拟议的研究将采用 SV40 小鼠肿瘤系统来评估 CTL 转移疗法和基于肽的疫苗的功效旨在 针对体内表达 SV40 标签的肿瘤的免疫反应。 简要地， SV40标签特异性CTL将通过Balb/c小鼠的免疫产生 SV40标签基因构建体和表位特异性通过使用确定 选定代表潜在 CTL 的 H-2d 限制性合成肽 SV40 标签上的表位。这些 CTL 将用于检查 过继转移 T 细胞以防止肿瘤挑战 同基因小鼠。 此外，还将检查选定的合成肽 体内主动诱导保护性肿瘤免疫的能力。 完成这项研究将为积极的活动提供有价值的信息 诱导涉及 SV40 标签表位特异性的肿瘤破坏性免疫 体内CTL。 此外，使用小鼠 SV40 生成的信息 肿瘤模型将加快试剂研发和临床试验 旨在检查 SV40 相关的 SV40 标签特异性免疫疗法 人类恶性肿瘤。