CELLULAR CANCER VACCINES--GPI PROTEIN TRANSFER

本提案涉及糖基的实际应用-- 磷脂酰肌醇(GPI)蛋白转导的研究进展 朝着临床翻译的方向前进。总体目标是 开发使用基因工程肿瘤的癌症免疫疗法 细胞本身(涂有共刺激分子-GPI蛋白，如 B7-1-GPI和B7-2-GPI)或抗原学工程专业人员 抗原提呈细胞(APC)(涂有MHC-GPI。肿瘤多肽 抗原复合体)作为细胞疫苗诱导全身抗肿瘤 回应。数据方面的成就有助于使用 蛋白质转移作为一种工具来生产每种类型的细胞 疫苗。值得注意的是，蛋白质转移与基因转移不同， 适用于原代肿瘤细胞和专业APC的现实情况 难以转化，便于同时表达 细胞表面有多种蛋白质。目前的提议包括 五种特定的急性心肌梗死被认为是癌症的平台 佐剂性癌症的治疗进展和后来的临床试验 疫苗：(1)B7-1GPI和B7-2-GPI的体外和体内研究 蛋白质将是完整的；(2)其他(非B7)的有用性 造口。用于免疫原性肿瘤细胞工程的GPIs，以及 其他潜在的代理人，将被评估；(3) 在肿瘤床内原位产生免疫原性肿瘤细胞将是 已确定；(4)人类白细胞抗原-A2.1‘GPI的功能研究 进行明确的肿瘤多肽抗原；和(5) 关于GPI蛋白转移本身的其他开发工作将是 已执行。

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.