突变增加用于中和血管内皮生长因子的可变新抗原受体单域抗体。
mutations increase variable new-antigen receptor single-domain antibodies for VEGF neutralization.
作者信息
Millán-Gómez Dalia, Dueñas Salvador, Muñoz Patricia L A, Camacho-Villegas Tanya, Elosua Carolina, Cabanillas-Bernal Olivia, Escalante Teresa, Perona Almudena, Abia David, Drescher Florian, Fournier Pierrick G J, Ramos Marco A, Mares Rosa E, Paniagua-Solis Jorge, Mata-Gonzalez Teresa, Gonzalez-Canudas Jorge, Hoffman Robert M, Licea-Navarro Alexei, Sánchez-Campos Noemí
机构信息
Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada, Baja California, México.
Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, Tijuana, Baja California, México.
出版信息
Oncotarget. 2018 Jun 15;9(46):28016-28029. doi: 10.18632/oncotarget.25549.
The stability, binding, and tissue penetration of variable new-antigen receptor (VNAR) single-domain antibodies have been tested as part of an investigation into their ability to serve as novel therapeutics. V13 is a VNAR that recognizes vascular endothelial growth factor 165 (VEGF). In the present study V13 was used as a parental molecule into which we introduced mutations designed . Two of the designed VNAR mutants were expressed, and their ability to recognize VEGF was assessed and . One mutation (Pro98Tyr) was designed to increase VEGF recognition, while the other (Arg97Ala) was designed to inhibit VEGF binding. Compared to parental V13, the Pro98Tyr mutant showed enhanced VEGF recognition and neutralization, as indicated by inhibition of angiogenesis and tumor growth. This molecule thus appears to have therapeutic potential for neutralizing VEGF in cancer treatment.
作为对可变新抗原受体（VNAR）单域抗体作为新型治疗药物能力研究的一部分，已对其稳定性、结合能力和组织穿透性进行了测试。V13是一种识别血管内皮生长因子165（VEGF）的VNAR。在本研究中，V13被用作亲本分子，我们在其中引入了设计好的突变。表达了两个设计好的VNAR突变体，并评估了它们识别VEGF的能力 以及 。一个突变（Pro98Tyr）旨在增强对VEGF的识别，而另一个突变（Arg97Ala）旨在抑制VEGF结合。与亲本V13相比，Pro98Tyr突变体表现出增强的VEGF识别和中和能力，这通过抑制血管生成和肿瘤生长得以体现。因此，该分子在癌症治疗中似乎具有中和VEGF的治疗潜力。
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