**Background**
Vascular endothelial growth factor A (VEGF-A) is a critical mediator of angiogenesis, the process by which new blood vessels form from pre-existing ones. Overexpression of VEGF-A is frequently observed in various malignancies, where it promotes tumor growth, survival, and metastasis by stimulating the proliferation and migration of endothelial cells. Consequently, targeting the VEGF-A pathway has become a cornerstone of therapeutic strategies to inhibit tumor vascularization and starve cancer cells of essential nutrients. Given its pivotal role in tumor progression, VEGF-A is a high-priority target for the development of potent neutralizing agents. In this context, we will introduce a high-affinity anti-VEGF-A antibody fragment – Brolucizumab.
**Definition**
Brolucizumab (also known as DLX1008) is a single-chain anti-VEGF-A antibody fragment (scFv-kappa-heavy) characterized by low picomolar affinity, with a dissociation constant (KD) of 1.05 pM.
**In Vitro and In Vivo Studies**
According to the Brolucizumab description, this molecule is designed to bind with high potency to VEGF-A to block its signaling cascade. Brolucizumab in vitro studies demonstrated that at a concentration of 2683 nM, the fragment inhibits VEGF-A112-induced phosphorylation of VEGFR1 in U87MG human glioma cells and phosphorylation of VEGFR2 in ZHE-483-2 GMEC. Furthermore, the Brolucizumab biological activity has been validated through binding assays, where immobilized human VEGF165 protein binds to Brolucizumab with an EC50 of 102.2 ng/mL.
Brolucizumab In Vivo research has highlighted its significant antitumor potential across different models. In U87MG glioma models, administration of Brolucizumab (5-50 mg/kg; i.p. once or twice daily for 28 days) resulted in delayed tumor growth. Additionally, in NSG mice subcutaneously injected with mSLK-KSHV cell suspensions, Brolucizumab (15 mg/kg; i.p. 5 days per week for 21 or 41 days) significantly lowered tumor growth, although no difference in survival was observed between experimental and combined control groups. Pharmacokinetic data in mice indicate a rapid decline phase half-life of 5.4-7.8 minutes and a slow decline phase half-life of 1.4-1.9 hours following i.v. administration at 10 mg/kg. In conclusion, Brolucizumab is a potent anti-VEGF-A antibody fragment that effectively inhibits angiogenesis and suppresses tumor growth in Brolucizumab Cancer research models.
Keywords
Brolucizumab, 1531589-13-5, DLX1008, ESBA 1008, RTH258, DLX 1008, DLX-1008, ESBA1008, ESBA-1008, RTH 258, RTH-258, VEGFR, Vascular endothelial growth factor receptor
References
[1] Szabó E, et, al. Antitumor Activity of DLX1008, an Anti-VEGFA Antibody Fragment with Low Picomolar Affinity, in Human Glioma Models. J Pharmacol Exp Ther. 2018 May;365(2):422-429.
[2] Eason AB, et, al. DLX1008 (brolucizumab), a single-chain anti-VEGF-A antibody fragment with low picomolar affinity, leads to tumor involution in an in vivo model of Kaposi Sarcoma. PLoS One. 2020 May 14;15(5):e0233116.