In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies

Abstract

<strong><em>Objective(s)</em></strong>: Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF) is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs) are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size and good penetration to tumor tissues makes them promising tools in drug development. Development of NBs targeting both human and mouse VEGF is required for understanding their <em>in vivo</em> functions. Therefore, development of cross-species reactive anti-VEGF Nbs for immunotherapy of lung cancer was the main aim of the current study.<br /> <strong><em>Materials and Methods: </em></strong>Here we developed NBs from <em>Camelus </em><em>dromedarius</em> library with high specificity and binding affinity to both human and mouse VEGF. <em>In</em> <em>vitro</em> and <em>In vivo</em> function of developed NB was evaluated on human endothelial cells and lung epithelial tumor cells (TC-1).<br /> <strong><em>Results:</em></strong> A nanobody showed the highest affinity to human and mouse VEGF and potently inhibited VEGF in the ELISA experiment. Anti-VEGF NBs significantly inhibited <em>in vitro</em> human endothelial cell migration through blockade of VEGF (<em>P</em>=0.045). Anti-VEGF NBs also significantly inhibited <em>in vivo</em> TC-1 growth in a dose-dependent manner (<em>P</em>=0.001) and resulted in higher survival rate in the nanobody treated group<br /> <strong><em>Conclusion:</em></strong> These findings demonstrate the potential of anti-VEGF NBsin tumor growth inhibition and are promising as novel cancer therapeutic candidate.