耐受蛋白酶切割的志贺毒素a亚基效应子多肽和包含其的细胞靶向分子

文档序号:431195 发布日期:2021-12-24 浏览:9次 >En<

阅读说明:本技术 耐受蛋白酶切割的志贺毒素a亚基效应子多肽和包含其的细胞靶向分子 (Shiga toxin a subunit effector polypeptides resistant to protease cleavage and cell targeting molecules comprising the same ) 是由 埃里克·波马 埃林·威勒特 杰克·希金森 贾森·金 于 2015-06-10 设计创作,主要内容包括:本发明提供能够表现出有效的志贺毒素功能(例如,亚细胞路线递送和细胞毒性)的包含志贺毒素效应子多肽的耐受蛋白酶切割的分子。本发明也提供用于靶向特定细胞型(例如,感染的或恶性细胞)的耐受蛋白酶切割的、细胞靶向的分子。本发明的某些分子是细胞毒性的,并且本发明的某些细胞靶向分子可以用于靶向性杀死特定的细胞型和治疗多种疾病、病症和病患,包括癌症、肿瘤、生长异常、免疫病症和微生物感染。与包含蛋白酶切割敏感性的野生型志贺毒素效应子多肽的相关细胞靶向分子相比,本发明的某些细胞靶向分子表现出改善的体内耐受性。本发明的细胞靶向分子可以将另外的物质(诸如,例如,抗原,细胞毒性剂和检测促进剂)递送到靶细胞内部。(The present invention provides protease cleavage resistant molecules comprising shiga toxin effector polypeptides capable of exhibiting potent shiga toxin functions (e.g., subcellular route delivery and cytotoxicity). The invention also provides protease cleavage resistant, cell-targeted molecules for targeting specific cell types (e.g., infected or malignant cells). Certain molecules of the invention are cytotoxic, and certain cell-targeting molecules of the invention can be used for targeted killing of specific cell types and treatment of a variety of diseases, disorders, and conditions, including cancer, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeting molecules of the invention exhibit improved in vivo tolerance compared to related cell-targeting molecules comprising protease cleavage sensitive wild-type shiga toxin effector polypeptides. The cell-targeting molecules of the present invention can deliver additional substances (such as, for example, antigens, cytotoxic agents, and detection promoters) to the interior of the target cell.)

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