A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo |
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| Authors: | Hong Lin Huiling Zhang Jun Wang Meiping Lu Feng Zheng Changjun Wang Xiaojun Tang Ning Xu Renjie Chen Dawei Zhang Ping Zhao Jin Zhu Yuan Mao Zhenqing Feng |
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| Affiliation: | 1. Huadong Medical Institute of Biotechniques, Nanjing, China;2. The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China;3. Department of Otolaryngology‐Head and Neck Surgery, Jiangsu Provincial Hospital, Nanjing, China;4. Jiangsu Provincial Blood Center, Nanjing, China;5. Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing, China;6. Department of Hematology and Oncology, Jiangsu Provincial Hospital, Nanjing, China;7. Department of Otolaryngology‐Head and Neck Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;8. Department of Otolaryngology‐Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China;9. Van Andel Research Institute, Grand Rapids, MI, USA |
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| Abstract: | Human trophoblastic cell surface antigen 2 (Trop2) has been suggested as an oncogene, which is associated with the different types of tumors. In this study, a human Fab antibody against Trop2 extracellular domain was isolated from phage library by phage display technology, and characterized by ELISA, FACS, fluorescence staining and Western blotting analysis. MTT, apoptosis assay and wound healing assay were employed to evaluate the inhibitory effects of Trop2 Fab on breast cancer cell growth in vitro, while tumor‐xenograft model was employed to evaluate the inhibitory effects on breast cancer growth in vivo. The results showed that Trop2 Fab inhibited the proliferation, induced the apoptosis and suspended the migration of MDA‐MB‐231 cells in a dose dependent manner. The expression caspase‐3 was activated, and the expression of Bcl‐2 was reduced while that of Bax was elevated in MDA‐MB‐231 cells by treating with Trop2 Fab. In addition, Trop2 Fab inhibited the growth of breast cancer xenografts and the expression of Bcl‐2 was reduced while that of Bax was elevated in xenografts. Trop2 Fab, which was isolated successfully in this research, is a promising therapeutic agent for the treatment of Trop2 expressing breast cancer. |
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| Keywords: | Trop2 Fab phage display breast cancer |
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