In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 6، دوره 20، شماره 5، مرداد 2017، صفحه 489-496 اصل مقاله (1.12 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8672 | ||
| نویسندگان | ||
| vFatemeh Kazemi-Lomedasht v1؛ Kamran Pooshang-Bagheri1؛ Mahdi Habibi-Anbouhi2؛ Ensiyeh Hajizadeh-Safar2؛ Delavar Shahbazzadeh1؛ Hasan Mirzahosseini1؛ Mahdi Behdani* 1 | ||
| 1Biotechnology Research Center, Biotechnology Department, Venom & Biotherapeutics Molecules Lab., Pasteur Institute of Iran, Tehran, Iran | ||
| 2National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran | ||
| چکیده | ||
| Objective(s): 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 in vivo functions. Therefore, development of cross-species reactive anti-VEGF Nbs for immunotherapy of lung cancer was the main aim of the current study. Materials and Methods: Here we developed NBs from Camelus dromedarius library with high specificity and binding affinity to both human and mouse VEGF. In vitro and In vivo function of developed NB was evaluated on human endothelial cells and lung epithelial tumor cells (TC-1). Results: A nanobody showed the highest affinity to human and mouse VEGF and potently inhibited VEGF in the ELISA experiment. Anti-VEGF NBs significantly inhibited in vitro human endothelial cell migration through blockade of VEGF (P=0.045). Anti-VEGF NBs also significantly inhibited in vivo TC-1 growth in a dose-dependent manner (P=0.001) and resulted in higher survival rate in the nanobody treated group Conclusion: These findings demonstrate the potential of anti-VEGF NBsin tumor growth inhibition and are promising as novel cancer therapeutic candidate. | ||
| کلیدواژهها | ||
| Angiogenesis Immunotherapy؛ Lung cancer؛ Nanobody؛ Vascular Endothelial Growth Factor | ||
| مراجع | ||
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