kdr Antibody
Description
Introduction to KDR Antibodies
KDR (kinase insert domain receptor), also known as vascular endothelial growth factor receptor 2 (VEGFR2), is a tyrosine kinase receptor critical for angiogenesis. Anti-KDR antibodies are engineered to bind and neutralize KDR, primarily by blocking its interaction with vascular endothelial growth factor (VEGF) or inhibiting receptor dimerization . These antibodies are pivotal in treating conditions driven by pathological angiogenesis, including solid tumors, diabetic retinopathy, and age-related macular degeneration .
Mechanism of Action
Anti-KDR antibodies function through multiple mechanisms:
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VEGF Binding Inhibition: Antibodies like TTAC-0001 block VEGF-A, VEGF-C, and VEGF-D from binding to KDR’s extracellular domain (ECD), preventing receptor activation .
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Receptor Dimerization Disruption: Some antibodies interfere with KDR dimerization, a prerequisite for downstream signaling .
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Kinase Activity Suppression: Neutralization is often measured by inhibition of receptor phosphorylation, a key step in angiogenic signaling .
Cancer Treatment
KDR antibodies suppress tumor angiogenesis by targeting endothelial cells in the tumor microenvironment. Preclinical studies demonstrate efficacy against:
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Gastric Cancer: KDR antisense oligonucleotides reduced cell proliferation by 55% in vitro .
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Glioblastoma and Sarcomas: Antibodies inhibit VEGF-driven signaling, slowing tumor growth .
Ophthalmological Diseases
Anti-KDR agents are under investigation for diabetic retinopathy and age-related macular degeneration due to their ability to reduce abnormal neovascularization .
Affinity and Avidity
| Antibody | K<sub>d</sub> (nM) | Avidity (nM) | Target Domain |
|---|---|---|---|
| TTAC-0001 | 0.7–44 | <0.1 | ECD 1–3 |
| Humanized IgG | ≤1 | >0.1 | ECD 3 |
SPR (surface plasmon resonance) analyses reveal sub-nanomolar affinities for leading candidates .
Functional Assays
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VEGF Competition ELISA: TTAC-0001 inhibited VEGF-KDR binding by >90% at 10 nM .
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Phosphorylation Assays: Anti-KDR antibodies reduced receptor autophosphorylation by 70–85% in endothelial cells .
Antibody Engineering
Modern techniques enhance antibody specificity and efficacy:
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Phage Display: Used to isolate high-affinity scFv fragments targeting KDR’s ECD .
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Affinity Maturation: Error-prone PCR and chain shuffling optimize CDR regions, achieving K<sub>d</sub> values ≤1 nM .
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Bispecific Formats: Diabodies and triabodies show improved avidity and tumor penetration .
Challenges and Future Directions
While anti-KDR antibodies show promise, challenges include:
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Resistance Mechanisms: Tumor endothelial cells may upregulate alternative pro-angiogenic pathways.
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Delivery Optimization: Improving bioavailability in hypoxic tumor cores remains a hurdle.
Combination therapies with EGFR inhibitors or chemotherapy are under exploration to enhance efficacy .
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
