结合
抗体
渗透(战争)
药品
单域抗体
癌症研究
抗体-药物偶联物
化学
生物
药理学
免疫学
单克隆抗体
数学
运筹学
工程类
数学分析
作者
Yanling Wu,Quanxiao Li,Ker‐Wei Yu,Zhi Wang,Lei Cheng,Ji Li,Lulu Ding,Qianqian Wang,Yuanrong Cheng,Yaozhu Wei,Yuanlin Song,Zhenlin Yang,Chao Tu,Yu Ding,Tianlei Ying
标识
DOI:10.1016/j.ymthe.2022.04.013
摘要
The inefficient tumor penetration of therapeutic antibodies has hampered their effective use in treating solid tumors. Here, we report the identification of a fully human single-domain antibody (UdAb), designated as n501, targeting the oncofetal antigen 5T4. The high-resolution crystal structure indicates that n501 adopts a compact structure very similar to that of camelid nanobodies, and binds tightly to all eight leucine-rich repeats of 5T4. Furthermore, the UdAb n501 exhibits exceptionally high stability, with no apparent activity changes over 4 weeks of storage at various temperatures. Importantly, the UdAb-based antibody-drug conjugate (n501-SN38) showed much deeper tumor penetration, significantly higher tumor uptake, and faster accumulation at tumor sites than conventional IgG1-based antibody-drug conjugate (m603-SN38), resulting in improved tumor inhibition. These results highlight the potential of UdAb-based antibody-drug conjugates as a potential class of antitumor therapeutics with characteristics of high stability and strong tumor penetration for the effective treatment of solid tumors.
科研通智能强力驱动
Strongly Powered by AbleSci AI