CELLULAR CANCER VACCINES--GPI PROTEIN TRANSFER

细胞癌疫苗--GPI蛋白转移

• 批准号: 2896054
• 负责人: Mark L Tykocinski
• 金额: $ 25.95万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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/2896054
• 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.

该建议涉及糖基 - 的实际应用 phoshatidylinyolininolininol（GPI）蛋白转剂，带有目标齿轮 迈向临床翻译。 总体目标是 开发用于使用EITH工程肿瘤的癌症的免疫疗法 细胞本身（用Costimulator-GPI蛋白绘画，例如 B7-1-GPI和B7-2-GPI）或抗原工程专业人员 抗原呈递细胞（APC）（用MHC-GPI涂漆。肿瘤肽 抗原复合物）作为细胞疫苗，以引起全身抗肿瘤 回答。 数据的成就有助于使用 蛋白质转移作为产生每种细胞的工具 疫苗。 重要的是，与基因转移不同，蛋白质转移是 现实适用于原发性肿瘤细胞和专业APC 很难转染和协助同时表达 细胞表面的多种蛋白质。目前的建议包括 五个特定的AMI，旨在作为癌症的平台 治疗性开发和随后的辅助癌临床试验 疫苗：（1）用B7-1GPI和B7-2-GPI进行体内和体内研究 蛋白质将完成； （2）其他（非B7）的有用性 costomulator.gpis用于免疫原性细胞工程，以及 将评估其他潜在的代理； （3） 在肿瘤床内的原位产生免疫原性肿瘤细胞将是 决定; （4）HLA-A2.1'GPIS轴承的功能研究 将进行明确定义的肿瘤肽抗原； （5） 关于GPI蛋白转移本身的其他开发工作将是 执行。