the development and characterization of a human mesothelioma in vitro 3d model to investigate immunotoxin therapy人类的发展和表征间皮瘤体外三维模型探讨抗毒素治疗.pdf

The Development and Characterization of a Human Mesothelioma In Vitro 3D Model to Investigate Immunotoxin Therapy 1. 1. 1 2 1 Xinran Xiang , Yen Phung , Mingqian Feng , Kunio Nagashima , Jingli Zhang , V. Courtney 3 1 1 1 Broaddus , Raffit Hassan , David FitzGerald , Mitchell Ho * 1 Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Science Applications International Corporation-Frederick, Inc., Frederick, Maryland, United States of America, 3 Lung Biology Center, University of California San Francisco, San Francisco, California, United States of America Abstract Background: Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates. Tumor microenvironments, however, are difficult to study in vitro. Cells cultured as monolayers exhibit less resistance to therapy than those grown in vivo and an alternative research model more representative of the in vivo tumor is more desirable. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing clinical trials in mesothelioma. Methodology/Principal Findings: Here, we examined how the tumor microenvironment affects the penetration and killing activity of SS1P in a new three-dimensional (3D) spheroid model cultured in vitro using the human mesothelioma cell line (NCI-H226) and two primary cell lines isolated from the ascites of malignant mesothelioma patients. Mesothelioma cells grown as monolayers or as spheroids expressed comparabl