title: A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo.
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.
authors: Huadong Medical Institute of Biotechniques, Nanjing, China; 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; Department of Otolaryngology-Head and Neck Surgery, Jiangsu Provincial Hospital, Nanjing, China; Jiangsu Provincial Blood Center, Nanjing, China.
authors: Hong
authors: H
authors: Lin
authors: Huiling
authors: H
authors: Zhang
authors: Jun
authors: J
authors: Wang
authors: Meiping
authors: M
authors: Lu
authors: Feng
authors: F
authors: Zheng
authors: Changjun
authors: C
authors: Wang
authors: Xiaojun
authors: X
authors: Tang
authors: Ning
authors: N
authors: Xu
authors: Renjie
authors: R
authors: Chen
authors: Dawei
authors: D
authors: Zhang
authors: Ping
authors: P
authors: Zhao
authors: Jin
authors: J
authors: Zhu
authors: Yuan
authors: Y
authors: Mao
authors: Zhenqing
authors: Z
authors: Feng
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; C494826:BAX protein, human; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C499380:TACSTD2 protein, human; D051028:bcl-2-Associated X Protein
keywords: Fab; Trop2; breast cancer; phage display