Inhibition of angiogenesis by a novel neutralizing antibody targeting human VEGFR-3

Abstract

Vascular endothelial growth factor receptor 3 (VEGFR-3) is a receptor for the vascular endothelial growth factor C and D (VEGF-C and D) and plays a critical role in the development of embryonic vascular system and regulation of tumor lymphangiogenesis. In this report, we generated a novel panel of 17 monoclonal antibodies (mAbs) against human VEGFR-3 and determined their ability to inhibit the proliferation of human erythroleukemia (HEL) cells and angiogenesis of chick embryo chorioallantoic membrane (CAM). Among these mAbs, BDD073 was demonstrated to inhibit the interaction of soluble VEGFR-3 with VEGF-D and the proliferation of HEL cells. Furthermore, in chick embryo CAM angiogenesis experiments, the angiogenesis induced by recombinant glutathione-S-transferase-VEGF-D was decreased in the presence of antibody BDD073. These data suggest that this novel neutralizing antibody against human VEGFR-3 could be a tool for the investigations into the biology of VEGFR-3, and potentially a reagent for blocking VEGF-D-induced angiogenesis and lymphogenesis.

Orbital lymphaticovenous malformations: Current and future treatments

“…107 These processes are also active in tumor lymphangiogenesis, 104,171 and in these circumstances, VEGF-C also leads to dilatation of the lymph vessels, assuring the lymphatic drainage from the tumor. 25 The second lymphatic endothelial cell-specific growth factor, VEGF-D, shares approximately 61% amino acid homology with VEGF-C and also binds to VEGFR-3 for its function. 1 Similar to VEGF-C, overexpression of VEGF-D in transgenic mouse skin also induces lymphangiogenesis.…”

“…The visual acuity was 20/30 in the right eye and 20/70 in the left eye with a minimal cataract. Examination of extraocular motility revealed limitation in upgaze to 25 and abduction to 20 . Hertel exophthalmometry was 18 mm in the right eye and 33 mm in the left eye (base 103 mm), with 3 mm downward displacement and an interpalpebral fissure of 12 mm.…”

VEGFR3 inhibition chemosensitizes lung adenocarcinoma A549 cells in the tumor-associated macrophage microenvironment through upregulation of p53 and PTEN

“…Preclinical evidence supports VEGFR3 as a clinical target. VEGFR3 inhibitors have been found to both inhibit angiogenesis/lymphangiogenic activities and decrease metastases ( 18 , 44 , 45 ). Notably, a soluble version of VEGFR3 has been identified ( 46 ).…”

Novel small peptides derived from VEGF125-136: potential drugs for radioactive diagnosis and therapy in A549 tumor-bearing nude mice

“…As the VEGF/VEGFR pathway is mainly responsible for tumor angiogenesis, VEGFRs are the most important factors contributing to tumor growth, angiogenesis and lymphangiogenesis. Targeting tumor angiogenesis has been approached through monoclonal antibodies that block VEGF-VEGFR binding 15 – 17 , and several drugs that block the VEGF/VEGFR pathway, such as bevacizumab and ramucirumab, have been approved by the FDA for treatment of common solid tumors 18 – 21 . However, major limitations of angiogenesis inhibitors have been observed by continued clinical investigations, such as resistance, enhancing tumor hypoxia and reducing the delivery of chemotherapeutic agents, which might be the main reasons for poor improvement after the clinical administration of angiogenesis inhibitors 22 .…”