Oncotarget

Research Papers:

The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer

Yuan Mao _, Xiaoying Wang, Feng Zheng, Changjun Wang, Qi Tang, Xiaojun Tang, Ning Xu, Huiling Zhang, Dawei Zhang, Lin Xiong, Jie Liang and Jin Zhu

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Oncotarget. 2016; 7:24810-24823. https://doi.org/10.18632/oncotarget.8529

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Abstract

Yuan Mao1, Xiaoying Wang2,3, Feng Zheng2, Changjun Wang2, Qi Tang3, Xiaojun Tang3, Ning Xu3, Huiling Zhang4, Dawei Zhang5, Lin Xiong6, Jie Liang7, Jin Zhu2,3

1Department of Oncology, Jiangsu Province Geriatric Hospital, Nanjing 210024, China

2Huadong Medical Institute of Biotechniques, Nanjing 210002, China

3Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China

4Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China

5Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China

6Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China

7Department of Pathology, Wuxi Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China

Correspondence to:

Yuan Mao, e-mail: ymaoent@yahoo.com

Jin Zhu, e-mail: zhujin1968@njmu.edu.cn

Keywords: Trop2, Fab, DOX, ADC, pancreatic carcinoma

Received: January 14, 2016     Accepted: February 28, 2016     Published: April 01, 2016

ABSTRACT

Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act oncogenically. In this study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed to evaluate the relationship between Trop2 expression and the clinicopathological features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence assay. MTT and wound healing analyses were used to evaluate the inhibitory effect of Trop2Fab-DOX on PC cell growth in vitro, while xenograft nude mice model was established to examine the tumor-inhibitory effects of PC in vivo. High Trop2 expression was observed in PC tissues and Trop2 expression was associated with several malignant attributes of PC patients, including overall survival. Trop2Fab-DOX can bind to the Trop2-expressing PC cells and provide an improved releasing type of DOX. In addition, Trop2Fab-DOX inhibited the proliferation and suppressed the migration of PC cells in a dose-dependent manner in vitro, while inhibited the growth of PC xenografts in vivo. Trop2 is a specific marker for PC, and a novel Trop2Fab-DOX ADC has a potent antitumor activity


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