Elmira Karami1, Shamsi Naderi1, Reyhaneh Roshan1, Mahdi Behdani1, Fatemeh Kazemi-Lomedasht2. 1. Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. 2. Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. fa_kazemi@pasteur.ac.ir.
Abstract
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.
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.
Authors: L G Frenken; R H van der Linden; P W Hermans; J W Bos; R C Ruuls; B de Geus; C T Verrips Journal: J Biotechnol Date: 2000-02-28 Impact factor: 3.307
Authors: Karim Bedjeguelal; Hugues Bienaymé; Antoine Dumoulin; Stéphane Poigny; Philippe Schmitt; Eric Tam Journal: Bioorg Med Chem Lett Date: 2006-06-09 Impact factor: 2.823