Human Non-Small Cell Lung Cancer-Chicken Embryo Chorioallantoic Membrane Tumor Models for Experimental Cancer Treatments

Abstract

To promote the preclinical development of new treatments for non-small cell lung cancer (NSCLC), we established NSCLC xenograft tumor assays on the chorioallantoic membrane (CAM) of chicken embryos. Five NSCLC cell lines were compared for tumor take rate, tumor growth, and embryo survival. Two of these, A549 and H460 CAM tumors, were histologically characterized and tested for susceptibility to systemic chemotherapy and gene delivery using viral vectors. All cell lines were efficiently engrafted with minimal effect on embryo survival. The A549 cells formed slowly growing tumors, with a relatively uniform distribution of cancer cells and stroma cells, while the H460 cells formed large tumors containing mostly proliferating cancer cells in a bed of vascularized connective tissue. Tumor growth was inhibited via systemic treatment with Pemetrexed and Cisplatin, a chemotherapy combination that is often used to treat patients with advanced NSCLC. Lentiviral and adenoviral vectors expressing firefly luciferase transduced NSCLC tumors in vivo. The adenovirus vector yielded more than 100-fold higher luminescence intensities after a single administration than could be achieved with multiple lentiviral vector deliveries. The adenovirus vector also transduced CAM tissue and organs of developing embryos. Adenovirus delivery to tumors was 100–10,000-fold more efficient than to embryo organs. In conclusion, established human NSCLC-CAM tumor models provide convenient in vivo assays to rapidly evaluate new cancer therapies, particularly cancer gene therapies.