Targeted therapy of angiogenesis using anti-VEGFR2 and anti-NRP-1 nanobodies

• Published in: Cancer chemotherapy and pharmacology Vol. 89; no. 2; pp. 165 - 172
• Main Authors: Karami, Elmira, Naderi, Shamsi, Roshan, Reyhaneh, Behdani, Mahdi, Kazemi-Lomedasht, Fatemeh
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2022; Springer Nature B.V
• Subjects: Angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Animals; Cancer Research; Cell proliferation; Cell Proliferation - drug effects; Chorioallantoic Membrane; Endothelial cells; HCT116 Cells; Human Umbilical Vein Endothelial Cells; Humans; Medicine; Medicine & Public Health; Mice; Mice, Nude; Molecular Targeted Therapy; Nanobodies; Neovascularization, Pathologic - therapy; Neuropilin; Neuropilin-1 - antagonists & inhibitors; Oncology; Original Article; Pharmacology/Toxicology; Single-Domain Antibodies - administration & dosage; Single-Domain Antibodies - pharmacology; Tumors; Vascular endothelial growth factor; Vascular endothelial growth factor receptor 2; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascularization; VEGFR2; Nanobody; NRP-1; Combination therapy; Target therapy
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-021-04372-5

Purpose Targeted therapy in cancer researches is a promising approach that can resolve drawbacks of systematic therapeutics. Nanobodies are potent therapeutics due to their high specificity and affinity to the target. Methods In this study, we evaluated the effect of the combination of anti-vascular endothelial growth factor receptor 2 (anti-VEGFR2) and anti-neuropilin-1 (anti-NRP1) nanobodies both in vitro (MTT, and tube formation assay) and in vivo (chick chorioallantoic membrane (CAM), and Nude mice treatment assay). Results Our results showed that the combination of two nanobodies (anti-VEGFR2/NRP-1 nanobodies) significantly inhibited proliferation as well as tube formation of human endothelial cells effective than a single nanobody. In addition, the mixture of both nanobodies inhibited vascularization of chick chorioallantoic membrane ex ovo CAM assay as compared to a single nanobody. Moreover, the mixture of both nanobodies significantly inhibited tumor growth of the mice (tumor volume and weight) higher than individual nanobodies ( P  < 0.05). Conclusion Our results offer a promising role of combination therapies in cancer therapy as well as angiogenesis.