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纤维连接蛋白(fibronectin,FN)的B结构域(extra-domain B,ED-B)作为新的实体肿瘤组织标志物已成为新药开发的优良靶点之一,已有多个抗体药物进入临床研究阶段。其中两项Ⅱ期临床试验数据显示B结构域的抗体融合蛋白(L19-IL2和L19-TNFα)对黑素瘤的疗效显著优于PD-1药物,相关Ⅲ期临床试验也已顺利开展。本文介绍B结构域的生物学特征、新药开发案例和潜在的开发方向,包括蛋白质药物结构改造与修饰、多种药物融合蛋白、适应证拓展、伴随诊断与个体化治疗等,也探讨加强源头创新以扩大新药研发差异化的方法,期望找到新的靶向药物开发热点。
As a new solid tumor tissue marker, extracellular domain B (ED-B) of fibronectin (FN) has become an excellent target for the development of new drugs. A number of antibody drugs have entered the clinical study stage. Two of these Phase II clinical trials showed that the B-domain antibody fusion proteins (L19-IL2 and L19-TNFα) were significantly more potent against melanoma than PD-1 and the Phase III clinical trials were well under way. This article describes the biological characteristics of B domain, the development of new drugs and potential development direction, including the transformation and modification of protein and drug structure, a variety of drug fusion proteins, indications expansion, with diagnosis and individualized treatment, but also to explore ways to strengthen the source of innovation In order to expand the differentiation of new drug research and development, expect to find a new target drug development hot spots.