title: The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer.
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.
authors.affiliation: Department of Oncology, Jiangsu Province Geriatric Hospital, Nanjing 210024, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.|Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Pathology, Wuxi Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.|Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D018796:Immunoconjugates; C544766:TROP2 protein, mouse
keywords: ADC; DOX; Fab; Trop2; pancreatic carcinoma