<Cancer Cell>: 赫尔辛基生物医学研究所的郑玮博士参与研究的抑制淋巴管生成项目取得突破性进展。
淋巴管生成在肿瘤发生等诸多生理病理机制中起到重要作用，其中，淋巴管生成因子与其受体在淋巴管生成中扮演了关键角色。该项目研制出一株新型抗体，可以通 过阻断血管生成因子受体3（VEGFＲ3）二聚体聚合的方式抑制淋巴管的生成。不同于传统的抑制配体－受体结合的抗体，该抗体在高浓度配体的情况下依然能 有效地抑制ＶＥＧＦＲ3的活性。更重要的是，与单独使用任意一种抗体比起来，该抗体与传统抗体的联合应用，在体外和动物实验中均显示出对淋巴生成具有更为 强烈的抑制性。因此该抗体在医学上具有很高的潜在价值，可用于治疗淋巴管相关的疾病。该项成果在淋巴管生成领域的处于世界领先水平，并与2010年11月 发表在国际顶级学术杂志《癌细胞》（《Cancer Cell》，影响因子：25.28）上，郑玮博士为并列第二作者。
原文链接与概述：
Effective Suppression of Vascular Network Formation by Combination of Antibodies Blocking VEGFR Ligand Binding and Receptor Dimerization
Denis Tvorogov, Andrey Anisimov, Wei Zheng, Veli-Matti Leppänen, Tuomas Tammela, Simonas Laurinavicius, Wolfgang Holnthoner, Hanna Heloterä, Tanja Holopainen, Michael Jeltsch, Nisse Kalkkinen, Hilkka Lankinen, Päivi M. Ojala, and Kari Alitalo
Antibodies that block vascular endothelial growth factor (VEGF) have become an integral part of antiangiogenic tumor therapy, and antibodies targeting other VEGFs and receptors (VEGFRs) are in clinical trials. Typically receptor-blocking antibodies are targeted to the VEGFR ligand-binding site. Here the authors describe a monoclonal antibody that inhibits VEGFR-3 homodimer and VEGFR-3/VEGFR-2 heterodimer formation, signal transduction, as well as ligand-induced migration and sprouting of microvascular endothelial cells. Importantly, they show that combined use of antibodies blocking ligand binding and receptor dimerization improves VEGFR inhibition and results in stronger inhibition of endothelial sprouting and vascular network formation in vivo. These results suggest that receptor dimerization inhibitors could be used to enhance anti-angiogenic activity of antibodies blocking ligand binding in tumor therapy.
淋巴管生成在肿瘤发生等诸多生理病理机制中起到重要作用，其中，淋巴管生成因子与其受体在淋巴管生成中扮演了关键角色。该项目研制出一株新型抗体，可以通 过阻断血管生成因子受体3（VEGFＲ3）二聚体聚合的方式抑制淋巴管的生成。不同于传统的抑制配体－受体结合的抗体，该抗体在高浓度配体的情况下依然能 有效地抑制ＶＥＧＦＲ3的活性。更重要的是，与单独使用任意一种抗体比起来，该抗体与传统抗体的联合应用，在体外和动物实验中均显示出对淋巴生成具有更为 强烈的抑制性。因此该抗体在医学上具有很高的潜在价值，可用于治疗淋巴管相关的疾病。该项成果在淋巴管生成领域的处于世界领先水平，并与2010年11月 发表在国际顶级学术杂志《癌细胞》（《Cancer Cell》，影响因子：25.28）上，郑玮博士为并列第二作者。
原文链接与概述：
Effective Suppression of Vascular Network Formation by Combination of Antibodies Blocking VEGFR Ligand Binding and Receptor Dimerization
Denis Tvorogov, Andrey Anisimov, Wei Zheng, Veli-Matti Leppänen, Tuomas Tammela, Simonas Laurinavicius, Wolfgang Holnthoner, Hanna Heloterä, Tanja Holopainen, Michael Jeltsch, Nisse Kalkkinen, Hilkka Lankinen, Päivi M. Ojala, and Kari Alitalo
Antibodies that block vascular endothelial growth factor (VEGF) have become an integral part of antiangiogenic tumor therapy, and antibodies targeting other VEGFs and receptors (VEGFRs) are in clinical trials. Typically receptor-blocking antibodies are targeted to the VEGFR ligand-binding site. Here the authors describe a monoclonal antibody that inhibits VEGFR-3 homodimer and VEGFR-3/VEGFR-2 heterodimer formation, signal transduction, as well as ligand-induced migration and sprouting of microvascular endothelial cells. Importantly, they show that combined use of antibodies blocking ligand binding and receptor dimerization improves VEGFR inhibition and results in stronger inhibition of endothelial sprouting and vascular network formation in vivo. These results suggest that receptor dimerization inhibitors could be used to enhance anti-angiogenic activity of antibodies blocking ligand binding in tumor therapy.
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