Madec, Frederic,Lecane, Philip,Marks, Philip,Foster, Keith
申请号：
ES13167699
公开号：
ES2630080T3
申请日:
2009.11.17
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
A polypeptide, for use in the suppression or treatment of cancer by inhibiting the autocrine secretion of a cancer cell in a patient, in which the polypeptide comprises: (i) a non-cytotoxic protease, protease that is capable of cleaving a protein SNARE expressed in said cancer cell； (ii) a Rest of Addressing (TM) that is capable of binding to a Union Site in a cancer cell, a Union Site that is capable of undergoing endocytosis to be incorporated into an endosome in the cancer cell； and (iii) a translocation domain that is capable of translocating the protease from within an endosome, through the endosomal membrane and into the cytosol of the cancer cell； in which the polypeptide lacks the natural binding function of a clostridial neurotoxin Hcc domain that allows the clostridial neurotoxin to bind to nerve terminals in the neuromuscular junction； with the proviso that the cancer cell is not a neuroendocrine tumor cell； and with the proviso that the polypeptide is not a natural clostridial neurotoxin molecule； and wherein said expression of the SNARE protein is regulated upward in the type of cancer cell when compared to the expression of the SNARE protein in the same cell type in a non-cancerous state.Un polipéptido, para uso en la supresión o tratamiento del cáncer mediante la inhibición de la secreción autocrina de una célula cancerosa en un paciente, en el que el polipéptido comprende: (i) una proteasa no citotóxica, proteasa que es capaz de escindir una proteína SNARE expresada en dicha célula cancerosa； (ii) un Resto de Direccionamiento (TM) que es capaz de unirse a un Sitio de Unión en una célula cancerosa, Sitio de Unión que es capaz de experimentar endocitosis para ser incorporado en un endosoma en la célula cancerosa； y (iii) un dominio de translocación que es capaz de translocar la proteasa desde dentro de un endosoma, a través de la membrana endosomal y en el citosol de la célula cancerosa； en el que el polipéptido carece de la función de unión natural de
