Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA,
Curr Oncol Rep. 2015 Aug;17(8):35. doi: 10.1007/s11912-015-0459-8.
Adnectins are a family of binding proteins derived from the 10th type III domain of human fibronectin (10Fn3), which is part of the immunoglobulin superfamily and normally binds integrin. The 10Fn3 has the potential for broad therapeutic applications given its structural stability, ability to be manipulated, and its abundance in the human body. The most commonly studied adnectin is CT-322, which is an inhibitor of vascular endothelial growth factor receptor-2. A bispecific adnectin, El-Tandem, has also been developed and binds to epidermal growth factor receptor and insulin-like growth factor-1 receptor simultaneously. Pre-clinical studies have shown promising results in relation to reducing tumor growth, decreasing microvessel density, and promoting normalization of tumor architecture. The phase I trial with CT-322 demonstrates relatively low toxicities. However, the phase II study done with CT-322 in recurrent glioblastoma does not reveal as promising results.
黏附蛋白是一类从人纤维连接蛋白的第十型 III 结构域衍生而来的结合蛋白，该结构域属于免疫球蛋白超家族，通常与整合素结合。由于其结构稳定性、可操作性以及在人体内的丰富程度，第十型 III 结构域具有广泛的治疗应用潜力。最常被研究的黏附蛋白是 CT-322，它是血管内皮生长因子受体-2 的抑制剂。一种双特异性黏附蛋白 El-Tandem 也已被开发出来，它同时与表皮生长因子受体和胰岛素样生长因子-1 受体结合。临床前研究表明，它在减少肿瘤生长、降低微血管密度和促进肿瘤结构正常化方面有很好的效果。CT-322 的 I 期试验显示出相对较低的毒性。然而，CT-322 在复发性脑胶质瘤中的 II 期研究结果并不那么令人鼓舞。
