CELLULAR CANCER VACCINES--GPI PROTEIN TRANSFER

本建议涉及糖基的实际应用， 磷脂酰肌醇（GPI）蛋白转移，目的是 临床转化的可能性 总体目标是 开发癌症的免疫疗法， 细胞本身（涂有共刺激因子GPI蛋白，如 B7-1-GPI和B7-2-GPI）或抗原工程专业人员 抗原呈递细胞（APC）（涂有MHC-GPI。肿瘤肽 抗原复合物）作为细胞疫苗以引发全身性抗肿瘤 应答 数据方面的成就有助于使用 蛋白质转移作为一种工具， 疫苗。 值得注意的是，蛋白质转移与基因转移不同， 现实适用于原发性肿瘤细胞和专业APC， 很难理解，也很容易同时表达 细胞表面的多种蛋白质。本提案包括： 五种特定的AMIs，旨在作为癌症的平台， 辅助癌症的治疗学开发和后期临床试验 疫苗：（1）B7- 1 GPI和B7-2-GPI的离体和体内研究 蛋白质将完成;（2）其他（非B7）的有用性 用于免疫原性肿瘤细胞工程的GPIs，沿着 其他潜在的代理人，将进行评估;（3）的可行性， 在肿瘤床内原位产生免疫原性肿瘤细胞将是 （4）HLA-A2. 1 'GPIs基因的功能研究 将进行明确定义的肿瘤肽抗原;和（5） 关于GPI蛋白转移本身的额外开发工作将 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.