CELLULAR CANCER VACCINES--GPI PROTEIN TRANSFER

细胞癌疫苗--GPI蛋白转移

• 批准号: 2372175
• 负责人: Mark L Tykocinski
• 金额: $ 23.77万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2372175
• 关键词: MHC class II antigen; antigen presenting cell; biotechnology; cellular immunity; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; glycosylphosphatidylinositols; human tissue; immunoconjugates; immunomodulators; laboratory mouse; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; oncoproteins; protein engineering; transfection; tumor antigens; vaccine development

This proposal deals with practical applications of glycosyl- phoshatidylinositol (GPI) protein tranfer, with the objectives geares towards clinical translation down the road. The overall goal is to develop immunotherapies for cancer which which use eith engineered tumor cells themselves (painted with costimulator-GPI proteins, such as B7-1-GPI and B7-2-GPI) or antigenically engineered professional antigen-presenting cells (APCs)(painted with MHC-GPI. Tumor peptide antigen complexes) as cellular vaccines to elicit systemic anti-tumor responses. Accomplishments to data have contributed towards the use of protein transfer as a tool for producing each of these kinds of cellular vaccines. Significantly, protein transfer, unlike gene transfer, is reality applicable to primary tumor cells and professional APCs that are difficult to transfect and facilitaes the simultanceous expression of multiple proteins at the cell surface. The present proposal consists of five specific amis which are intended to serve as a platform for cancer therapeutics development and later clinical trials with adjuvant cancer vaccines: (1) ex vivo and in vivo studies with B7-1GPI and B7-2-GPI proteins will be completed; (2) The usefulness of other (non-B7) costomulator.GPIs for immunogenic tumore cell engineering, along with other potentially agents, will be evaluated; (3) The feasibilty of generating immunogenic tumor cells in the situ within tumor beds will be determined; (4) Functional studies with HLA-A2.1'GPIs bearing well-defined tumor peptide antigens will be conducted; and (5) Additional developmental work on GPI protein transfer per se will be performed.

该提案涉及糖基的实际应用 磷脂酰肌醇 (GPI) 蛋白质转移，目标齿轮 朝着临床转化的方向发展。 总体目标是 开发使用工程肿瘤的癌症免疫疗法 细胞本身（涂有共刺激 GPI 蛋白，例如 B7-1-GPI 和 B7-2-GPI) 或抗原工程专业 抗原呈递细胞（APC）（涂有MHC-GPI。肿瘤肽 抗原复合物）作为细胞疫苗来引发全身抗肿瘤 回应。 数据的成就促进了数据的使用 蛋白质转移作为产生每种细胞的工具 疫苗。 值得注意的是，与基因转移不同，蛋白质转移是 适用于原发性肿瘤细胞和专业 APC 的现实 难以转染并有利于同时表达 细胞表面有多种蛋白质。本提案包括 五个特定的 amis 旨在作为癌症平台 辅助癌症的疗法开发和后续临床试验 疫苗：(1) B7-1GPI 和 B7-2-GPI 的离体和体内研究 蛋白质将完成； （2）其他（非B7）的用处 用于免疫原性肿瘤细胞工程的 costomulator.GPI，以及 将评估其他潜在代理人； (3) 可行性 在肿瘤床内原位产生免疫原性肿瘤细胞将是 决定; (4) HLA-A2.1'GPI轴承的功能研究 将进行明确的肿瘤肽抗原；和（5） GPI 蛋白转移本身的其他开发工作将是 执行。