一种新型单链抗体将腺病毒重定向至表达IL13Rα2的脑肿瘤。
A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors.
作者信息
Kim Julius W, Young Jacob S, Solomaha Elena, Kanojia Deepak, Lesniak Maciej S, Balyasnikova Irina V
机构信息
The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
Biophysics Core Facility, The University of Chicago, Chicago, IL 60637, USA.
出版信息
Sci Rep. 2015 Dec 14;5:18133. doi: 10.1038/srep18133.
The generation of a targeting agent that strictly binds to IL13Rα2 will significantly expand the therapeutic potential for the treatment of IL13Rα2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13Rα2 monoclonal antibody and tested its binding properties. Furthermore, to demonstrate the potential therapeutic applicability of scFv47, we engineered an adenovirus by incorporating scFv47 as the targeting moiety in the viral fiber and characterized its properties in vitro and in vivo. The scFv47 binds to human recombinant IL13Rα2, but not to IL13Rα1 with a high affinity of 0.9 · 10(-9) M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13Rα2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13Rα2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13Rα2-expressing glioma and other malignancies.
生成一种能严格结合白细胞介素13受体α2（IL13Rα2）的靶向剂，将显著扩大治疗表达IL13Rα2癌症的治疗潜力。为实现这一目标，我们从亲本IL13Rα2单克隆抗体中生成了一种单链抗体（scFv47），并测试了其结合特性。此外，为证明scFv47的潜在治疗适用性，我们通过将scFv47作为靶向部分整合到病毒纤维中来构建腺病毒，并在体外和体内对其特性进行了表征。scFv47以0.9·10（-9）M的高亲和力与人重组IL13Rα2结合，但不与IL13Rα1结合，这与亲本抗体相似。此外，scFv47在体外和体内均成功地将腺病毒重定向至表达IL13Rα2的胶质瘤细胞。我们的数据证实scFv47是一种高度选择性的IL13Rα2靶向剂，并为进一步开发scFv47修饰的溶瘤腺病毒和其他治疗药物用于治疗表达IL13Rα2的胶质瘤和其他恶性肿瘤提供了依据。
Zotero 插件