GPI-ANCHORED MOLECULES AS THERAPEUTIC VACCINES

描述（改编自申请人的摘要）：通过以下修饰的肿瘤： 目前，共刺激分子（如B7.1）的基因转染正在进行中。 被认为是一种潜在的治疗性肿瘤疫苗。 然而，转染 并不总是有效的，并且对于许多细胞类型可能是困难的， 尤其是从患者新鲜分离的肿瘤细胞。 研究者 建议确定用共刺激修饰的肿瘤的功效， 分子使用一种新的方法。 研究表明，纯化的糖基 磷脂酰肌醇（GPI）锚定的细胞表面蛋白可以是 通过将蛋白质与蛋白质一起孵育， 细胞 这种独特的性质可用于重组细胞表面 在细胞膜上表达受体而不使用基因转染。 利用重组技术，他们构建并表达了 纯化的GPI锚定的B7.1分子对肿瘤的作用。 研究者建议 确定用以下物质重建的肿瘤的免疫原性潜力： GPI-B7诱导肿瘤特异性免疫。 使用体外人 实验和体内小鼠实验，诱导的最佳条件， 将测定肿瘤免疫。 他们还将确定细胞因子是否能增强诱导的免疫力。 通过GPI锚定分子修饰的肿瘤。 人类肿瘤细胞系将 开发用于确定GPI-B7.1重建对 自体肿瘤特异性CTL体外开发。 其它共刺激 粘附分子如GPI-ICAM-1和热稳定性抗原将被 单独或与B7.1联合开发和测试，用于诱导 肿瘤特异性免疫 拟议研究的结果将 证明GPI锚定的有效性和潜在应用 分子修饰的肿瘤作为肿瘤免疫治疗的治疗性疫苗。 从长远来看，从这项研究中获得的知识可以用于 开发一种治疗癌症的“人工细胞疫苗”。

DESCRIPTION (Adapted from the Applicant's Abstract): Tumors modified by transfecting genes for co-stimulatory molecules such as B7.1 are now being considered as a potential therapeutic tumor vaccine. However, transfection is not always efficient and can be difficult with many cell types, especially freshly isolated tumor cells from patients. The investigator proposes to determine efficacy of tumors modified with co-stimulatory molecules using a novel approach. Studies have shown that purified glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins can be spontaneously incorporated into cells by incubating the proteins with the cells. This unique property can be used to reconstitute cell surface expression receptors on cell membranes without the use of gene transfection. Using recombinant techniques, they have constructed and expressed the purified GPI-anchored B7.1 molecule on tumors. The investigator proposes to determine the immunotherapeutic potential of tumors reconstituted with GPI-B7 in inducing tumor specific immunity. Using in vitro human experiments and in vivo mouse experiments, optimal conditions for inducing tumor immunity will be determined. They will also determine whether cytokines can enhance the immunity induced by tumors modified with GPI-anchored molecules. Human tumor cell lines will be developed to determine the efficacy of GPI-B7.1 reconstitution on autologous tumor specific CTL development in vitro. Other co-stimulatory adhesion molecules such as GPI-ICAM-1 and heat-stable antigen will be developed and tested alone or in combination with B7.1, for the induction of tumor specific immunity. The results from the proposed research will demonstrate the efficacy and potential application of the GPI-anchored molecule modified tumors as a therapeutic vaccine for tumor immunotherapy. In the long term the knowledge obtained from this study could be used to develop an "artificial cell vaccine" to treat cancer.