VEGFR2 Specific Neutra™ Antibody Products

Vascular endothelial growth factor receptor 2 (VEGFR2), classified as a type IV receptor tyrosine kinase and also referred to as KDR, represents a key receptor for VEGF. Designated as a kinase insert domain receptor, VEGFR2 is a type III receptor tyrosine kinase pivotal in mediating VEGF-induced endothelial processes, including survival, proliferation, sprouting, and tubular morphogenesis. The intricate regulation of its signaling and trafficking involves multiple factors, such as P2Y purine nucleotide receptor, Rab GTPase, T-cell protein tyrosine phosphatase, and integrin alphaVbeta3, among others.

Its Gene ID: 3791, UniProtKB ID: P35968, and OMIM ID: 191306

The Signaling Pathway of VEGFR2

Autophosphorylation tyrosine residues and dimerization of VEGFR2 intracellular domain is mediated by VEGF, which binds to extracellular I-III Ig-like domains. Phosphorylation of tyrosine residues creates binding sites for SH2 domains of adapter proteins. Activation of PIP2 generates the second messengers DAG and IP3, the latter inducing the release of intracellular Ca2+ from the endoplasmic reticulum, a crucial regulator of intracellular signaling. DAG and Ca2+ activate PKC, subsequently triggering the Erk pathway. The binding of the cytoplasmic protein NCK1 to phosphorylated tyrosine activates a signal cascade involving small GTPase. Consequently, this intracellular signal transduction pathway leads to the proliferation and migration of endothelial cells, synthesis of anti-apoptotic proteins, and an increase in vascular permeability.

Fig.1 The VEGFR-VEGF signaling pathway.¹

Roles of Anti-VEGFR2 Antibodies and Agents in Cancer Treatment

The VEGFR/VEGF axis serves as a pivotal regulator of angiogenesis and represents a critical therapeutic target in cancer. The application of anti-VEGFR2 monoclonal antibodies (mAbs) has emerged as a key strategy for treating various cancers. Elevated circulating levels of VEGF following administration of anti-VEGFR2 mAbs have been linked to a poorer prognosis. This observation suggests that the excess VEGF induced by anti-VEGFR2 mAbs negatively impacts treatment efficacy, highlighting the potential for improved outcomes through the neutralization of VEGF. Creative Biolabs offers human anti-VEGFR2 mAb that can specifically bind to VEGFR2 such as Anti-VEGFR2 Neutralizing Antibody (V3S-0622-YC2786) and Recombinant Anti-VEGFR2 Antibody (V3S-0522-YC7914).

• Using antibodies for ligand-receptor dual blockade as a targeted anti-angiogenic strategy

Regulation of the VEGFR2/VEGF pathways involves a network of multiple ligands and receptors. This inherent redundancy underscores the physiological significance of angiogenesis, and the intricate interplay of various factors may contribute to tumors developing resistance to angiogenic inhibitors. In response to this phenomenon, the exploration of receptor-ligand dual blockade emerges as a promising combination strategy. Employing anti-VEGFR2 and anti-VEGF antibodies for the dual blockade of the VEGFR2/VEGF pathway notably restrained gastric tumor growth. Gene expression analysis unveiled a significant suppression of genes linked to angiogenesis and other tumor-promoting pathways with the application of this dual blockade therapy, as compared to the sole utilization of the anti-VEGFR2 antibody. This suggests that the dual-targeting of the ligand/receptor in this pathway guarantees specific anti-angiogenic effects, simultaneously curbing tumor progression and compensating for other modifications in cell signaling.

Fig.2 Molecular pathways affected by VEGFR2 and VEGF-A targeted therapy.²

Creative Biolabs unveils an extensive repertoire of intricately designed anti-VEGFR2 antibody products, meticulously crafted to drive advancements in research focused on therapeutic strategies addressing various facets of solid cancers and disorders related to neoplastic angiogenesis. Additionally, we eagerly welcome inquiries concerning the personalized customization of anti-VEGFR2 bispecific antibodies.

REFERENCES

1. Zhao, Yueshui, et al. "VEGF/VEGFR-targeted therapy and immunotherapy in non-small cell lung cancer: targeting the tumor microenvironment." International Journal of Biological Sciences 18.9 (2022): 3845.
2. Mashima, Tetsuo, et al. "Neutralization of the induced VEGF-A potentiates the therapeutic effect of an anti-VEGFR2 antibody on gastric cancer in vivo." Scientific Reports 11.1 (2021): 15125.