公开(公告)号：US20180015184A1

公开(公告)日：2018-01-18

申请号：US15208335

申请日：2016-07-12

申请人： Memorial Sloan-Kettering Cancer Center ,  Vascular Biogenics, Ltd.

发明人： Richard N. Kolesnick ,  Branka Stancevic ,  Michel Sadelain ,  Zvi Fuks ,  Nira Varda-Bloom ,  Dror Harats

IPC分类号： A61K48/00 ,  A61K38/46

CPC分类号： A61K48/0066 ,  A61K38/46 ,  A61K48/0058 ,  C12N2710/10343

摘要： Disclosed herein are methods and compositions for treating cancer by increasing radiation-induced damage to cancer without increasing radiation-induced side effects by increasing secretory ASMase levels specifically in tumor endothelium, and inducing apoptosis of tumor endothelial cells by treating the tumor with radiation. ASMase levels are increased in tumor endothelium by administration of a recombinant DNA construct comprising a region coding for a functional ASMase linked to particular transcriptional regulatory sequences that confer tissue-specific expression of ASMase.

公开(公告)号：US20170007718A1

公开(公告)日：2017-01-12

申请号：US14846513

申请日：2015-09-04

申请人： Memorial Sloan-Kettering Cancer Center

发明人： Richard N. Kolesnick ,  Branka Stancevic ,  Michel Sadelain ,  Zvi Fuks ,  Nira Varda-Bloom ,  Dror Harats

IPC分类号： A61K48/00 ,  C12N15/86 ,  C12N9/16 ,  A61K45/06

CPC分类号： A61K48/005 ,  A61K35/761 ,  A61K38/00 ,  A61K45/06 ,  A61N2005/1098 ,  C12N9/16 ,  C12N15/86 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/15 ,  C12N2830/85

摘要： Disclosed herein are methods and compositions for treating cancer by increasing radiation-induced damage to cancer without increasing radiation-induced side effects by increasing secretory ASMase levels specifically in tumor endothelium, and inducing apoptosis of tumor endothelial cells by treating the tumor with radiation. ASMase levels are increased in tumor endothelium by administration of a recombinant DNA construct comprising a region coding for a functional ASMase linked to particular transcriptional regulatory sequences that confer tissue-specific expression of ASMase.

摘要翻译： 本文公开了通过增加辐射诱导的癌症损伤而不增加辐射诱导的副作用的方法和组合物，通过在肿瘤内皮中特异性增加分泌型ASMase水平，并通过用辐射治疗肿瘤来诱导肿瘤内皮细胞的凋亡。 通过施用重组DNA构建体，ASMase水平增加，所述重组DNA构建体包含与赋予ASMase的组织特异性表达的特定转录调控序列连接的功能性ASMase的区域。