A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Western Blotting
2.3. In Vitro Angiogenesis Assay
2.4. Animals
2.5. Animal Model of Laser-Induced CNV
2.6. Combination Index (CI)
2.7. Immunohistochemistry and Terminal Deoxynucleotidyl Transferase dUTP Nick End-Labeling (TUNEL) Assay
2.8. Live and Dead Cell Double Staining Assay
2.9. Ocular Pharmacokinetics (PK)
2.10. Retinal Vascular Development
2.11. Statistical Analysis
3. Results
3.1. The Anti-cKIT Blocking IgG, NN2101, Inhibits SCF/cKIT-Mediated Angiogenic Signaling and Angiogenesis in Human Endothelial Cells at Hypoxia
3.2. Intravitreal Administration of NN2101 Suppresses SCF/cKIT Signaling and the Pathological CNV in a Murine Model of Neovascular AMD
3.3. A Combination Therapy of NN2101 and Aflibercept Additively Inhibits Pathological CNV in Mice
3.4. NN2101 Does Not Induce Ocular Toxicity
3.5. NN2101 Does Not Affect Early Retinal Vascular Development in Mice
3.6. PK of Intravitreal NN2101 in the Rabbit Eyes and Serum
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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PK Parameters | Vitreous | Aqueous | Retina/Choroid | Serum |
---|---|---|---|---|
T1/2, h | 103.3 | 203.0 | 128.9 | |
MRT, h | 131.3 | 208.5 | 243.7 | 311.6 |
V/F, mL | 1.3 | 12.0 | 98.1 | |
CL/F, mL/h | 0.009 | 0.041 | 0.527 | |
Cmax, μg/mL | 378.3 | 100.8 | 3.2 | 0.3 |
AUC, h × μg/mL | 63,921.0 | 12,771.9 | 1101.6 | 132.7 |
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Seo, S.; Kim, K.L.; Yeo, Y.; Kim, R.-I.; Jeong, H.; Kim, J.-O.; Song, S.-H.; An, M.-J.; Kim, J.-W.; Hong, H.K.; et al. A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice. Pharmaceutics 2021, 13, 1308. https://doi.org/10.3390/pharmaceutics13081308
Seo S, Kim KL, Yeo Y, Kim R-I, Jeong H, Kim J-O, Song S-H, An M-J, Kim J-W, Hong HK, et al. A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice. Pharmaceutics. 2021; 13(8):1308. https://doi.org/10.3390/pharmaceutics13081308
Chicago/Turabian StyleSeo, Songyi, Koung Li Kim, Yeongju Yeo, Ryul-I Kim, Hayoung Jeong, Jin-Ock Kim, Sun-Hwa Song, Mi-Jin An, Jung-Woong Kim, Hye Kyoung Hong, and et al. 2021. "A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice" Pharmaceutics 13, no. 8: 1308. https://doi.org/10.3390/pharmaceutics13081308
APA StyleSeo, S., Kim, K. L., Yeo, Y., Kim, R. -I., Jeong, H., Kim, J. -O., Song, S. -H., An, M. -J., Kim, J. -W., Hong, H. K., Ham, M. H., Woo, S. J., Sung, J. -H., Park, S. G., & Suh, W. (2021). A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice. Pharmaceutics, 13(8), 1308. https://doi.org/10.3390/pharmaceutics13081308