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

// Yuan Mao 1 , Xiaoying Wang 2, 3 , Feng Zheng 2 , Changjun Wang 2 , Qi Tang 3 , Xiaojun Tang 3 , Ning Xu 3 , Huiling Zhang 4 , Dawei Zhang 5 , Lin Xiong 6 , Jie Liang 7 , Jin Zhu 2, 3 1 Department of Oncology, Jiangsu Province Geriatric Hospital, Nanjing 210024, China 2 Huadong Medical Institute of Biotechniques, Nanjing 210002, China 3 Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China 4 Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China 5 Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China 6 Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China 7 Department 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