-
公开(公告)号：US08461311B2
公开(公告)日：2013-06-11
申请号：US13155577
申请日：2011-06-08
CPC分类号： C07K14/4747 , C07K14/52
摘要： Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic. acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.
摘要翻译： 公开了TNF相关凋亡诱导配体（TRAIL）三聚体（TR3）和编码共价连接的TRAIL三聚体的核酸。 与天然TRAIL相比，TRAIL三聚体可以具有更高的稳定性，并且可以保留TRAIL的天然杀伤能力。 可通过用可溶性死亡受体5（DR5-Fc）阻断其活性来显示TR3的靶特异性。 还公开了修饰的TRAIL三聚体和核酸。 编码它们的酸。 这些修饰包括额外的功能域，例如抗体片段（scFv）。 包含附加功能域的TR3可以允许TR3的细胞特异性递送。 本发明人公开了在胰腺癌模型中靶向细胞杀伤的TR3装饰的RBC。
-
公开(公告)号：US20110300629A1
公开(公告)日：2011-12-08
申请号：US13155577
申请日：2011-06-08
CPC分类号： C07K14/4747 , C07K14/52
摘要： Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. In some configurations, a modification such as the addition of a functional domain can be stoichiometrically controlled. In some configurations, a modification can be inconsequential with regard to the bioactivity of TRAIL. In various embodiments, a TR3, including a modified TR3, can be a cancer-selective drug. In some configurations, a TR3 that comprises an additional biologically active moiety such as a functional domain of a protein can have fewer off-target toxicities compared to TRAIL alone. In some configurations, a TR3 that comprises an additional biologically active moiety such as a functional domain of a protein can have enhanced killing capacities compared to the moiety alone. In some aspects, TR3 activity can be targeted to an RBC membrane. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.
摘要翻译： 公开了TNF相关凋亡诱导配体（TRAIL）三聚体（TR3）和编码共价连接的TRAIL三聚体的核酸。 与天然TRAIL相比，TRAIL三聚体可以具有更高的稳定性，并且可以保留TRAIL的天然杀伤能力。 可通过用可溶性死亡受体5（DR5-Fc）阻断其活性来显示TR3的靶特异性。 还公开了修饰的TRAIL三聚体和编码它们的核酸。 这些修饰包括额外的功能域，例如抗体片段（scFv）。 包含附加功能域的TR3可以允许TR3的细胞特异性递送。 在一些配置中，可以化学计量地控制诸如添加功能域的修饰。 在一些配置中，关于TRAIL的生物活性，修饰可能是无关紧要的。 在各种实施方案中，包括修饰的TR3的TR3可以是癌症选择性药物。 在一些配置中，与单独的TRAIL相比，包含另外的生物活性部分如蛋白质的功能结构域的TR3可以具有较少的靶外毒性。 在一些构型中，与单独的部分相比，包含另外的生物活性部分如蛋白质的功能结构域的TR3可以具有增强的杀伤能力。 在一些方面，TR3活性可以靶向RBC膜。 本发明人公开了在胰腺癌模型中靶向细胞杀伤的TR3装饰的RBC。
-
搜索结果
2 条记录 (耗时 0.024 秒)
