A Novel Vascular Endothelial Growth Factor trap KP-VR2 with Enhanced Ligand Blocking Volume 4 - Issue 4

VM.Molina*¹, J. Morales, MF¹, Gutierrez^2,3

• ¹Boehringer Ingelheim, Pet Technical Service, Colombia
• ²Clinic veterinary Campomaskotas. Colombia
• ³University of La Salle, Colombia

Received:March 03, 2021   Published: April 26, 2021

Corresponding author: VM. Molina, Boehringer Ingelheim, Pet Technical Service, Colombia

DOI: 10.32474/OAJOM.2021.04.000191

 

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Abstract

Antiangiogenic therapies targeting vascular endothelial growth factor (VEGF)-A have been commonly used to treat various cancers; however, their clinical efficacy remains limited due to resistance and activation of compensatory pathways resulting from elevated circulating VEGF-B and placental growth factor (PlGF) levels. Thus, we developed a novel VEGF-Trap, KP-VR2, which can neutralize VEGF-A, VEGF-B, and PlGF to mediate these problems. KP-VR2 consists of two consecutive second Ig-like domains (D2s) of VEGF receptor 1 (VEGFR-1) fused to human IgG1 Fc. KP-VR2 showed more potent decoy activity than the current VEGF-Trap against VEGF and PlGF. Most importantly, two consecutive D2s of VEGFR-1 can generate two putative binding sites, resulting in a significant improvement in binding capacity. These advances resulted in stronger antitumor efficacy in implanted tumor models than aflibercept and bevacizumab. Overall, the results of this study highlight KP-VR2 as a promising therapeutic candidate for further clinical drug development.

Abstract| Introduction| Results| Discussion| Experimental Procedures| Statistical Analyses| Data Availability Statement| Acknowledgements| Conflict of Interest| References|