Empowered by our advanced technique platforms and experienced experts, Creative Biolabs provides customized monoclonal antibody (mAb) development services against antigens in tumor stroma and vasculature to help your projects. Creative Biolabs offers a comprehensive set of antibody features analysis services against vascular endothelial growth factor receptor 2 (VEGFR2) to assist our clients determine the biochemical property and provide a guideline for project progression.
Angiogenesis, the formation of new blood vessels, is regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). Preclinical evidence suggest that antibodies targeting VEGFs may exert their activity throughout the inhibition of VEGFR2 phosphorylation, a key factor in the cancer angiogenic process. During cancer-induced angiogenesis, cancer cells secrete VEGFs that bind to VEGFR2, triggering a tyrosine kinase signaling cascade via the dimerization of VEGFR2. Consequently, the kinase signaling cascade stimulates the production of factors that variously stimulate vessel permeability, proliferation/survival, migration, and finally differentiation of mature blood vessels. VEGFR2 is available to mediate all known functions of VEGFs on vascular endothelial cells whereas VEGFR1 or VEGFR3 might play a minor or indirect role. VEGFR2 is strongly and consistently expressed on blood vessels in a variety of solid tumors. Treatment with anti-VEGFR2 antibodies had no effect on morphology or number of vessels in normal tissues, suggesting that anti-VEGFR2 antibodies could be used to deliver toxins, tissue factor, or radionuclides to tumor vasculature.
Fig.1 Representative structure of VEGF tyrosine kinase receptors. (McMahon, 2000)
The over-expression on the surface of tumor cells and tumor vascular endothelial cell has made VEGFR2 a highly desirable target for the development of both antiangiogenic and vascular targeting drugs. Therefore, different anti-angiogenic agents targeting the VEGF/VEGFR2 signaling cascade have been developed as cancer therapeutics. Some representative anti-angiogenic agents that inhibit VEGFR2-mediated signal transduction are shown in figure 2, such as ramucirumab (a fully humanized mAb targeting the extracellular domain of VEGFR2), bevacizumab (a humanized mAb targeting VEGF-A), and aflibercept (acting as a decoy receptor to block VEGF-A and VEGF-B). Besides individual mAb or chemical, antibody conjugates also wield their powerful effect on anti-tumor therapy. For instance, anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles, recombinant immunotoxin KPLK, and ADC V21-DOS47 all presented a significant antitumor effect both in vitro and in vivo while not showing obvious toxicity to normal cells and tissues, as paper reported. Among them, V21-DOS47 is composed of a camelid single domain antibody V21 and the enzyme urease. VEGF-VEGFR axis is an exciting and expanding area which is being translated into the next generation of therapeutics for major diseases.
Fig.2 Therapeutic inhibitors of VEGFR2 signal transduction (Smith, 2015)
Creative Biolabs is committed to providing high-quality antibody products and chemical synthesis services against VEGFR2 to promote the progress of your projects. Please contact us for more information and a detailed quote.
References
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