[EN] REPROGRAMMING UROKINASE INTO AN ANTIBODY-RECRUITING ANTICANCER AGENT<br/>[FR] REPROGRAMMATION DE L'UROKINASE EN UN AGENT ANTICANCÉREUX DE RECRUTEMENT D'ANTICORPS
申请人:UNIV YALE
公开号:WO2013070688A1
公开(公告)日:2013-05-16
The present invention relates to chimeric (preferably, bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit ovrexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds preferably covalently bind to the urokinase receptor and recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and/or antibody-dependent cellular cytotoxicity (ADCC) against a large number and variety of cancers, thus providing cancer cell death and/or an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.
本发明涉及嵌合(最好是双功能)化合物,包括这些化合物的组合物和治疗患者或受试者的癌症的方法,特别是包括转移性癌症,其中癌细胞表现出细胞表面尿激酶型纤溶酶原激活剂受体(尿激酶受体)的过度表达(高表达)与正常(非癌细胞)细胞相比。这些化合物最好与尿激酶受体共价结合,并招募患者或受试者的天然抗体,其中这些抗体可以通过抗体依赖性细胞吞噬和/或抗体依赖性细胞细胞毒作用(ADCC)选择性地降解和/或失活靶向癌细胞,针对大量和各种癌症,从而提供癌细胞死亡和/或抑制癌症的生长、发展和/或转移,包括患者癌症的缓解和治愈。