title: Cell Surface Antibody Retention Influences In Vivo Antitumor Activity Mediated by Antibody-dependent Cellular Cytotoxicity.
abstract: Multiple factors affect the in vivo antitumor activity of antibody-based therapeutics; however, the influence of cell surface retention on antibody-dependent cellular cytotoxicity (ADCC) is not fully understood. Here we evaluated the importance of cell surface antibody retention in antitumor activity mediated by ADCC in vivo.
  
  
  
  Two mAbs against tumor-associated calcium signal transducer 2 (TACSTD2/TROP2), AR47A6.4.2 and Pr1E11, were used. Antitumor activities against BxPC3 and Colo205 cells were investigated through in vitro and in vivo assays.
  
  
  
  Pr1E11 showed better cell surface retention than AR47A6.4.2 in vitro although Pr1E11 and AR47A6.4.2 showed equivalent ADCC activity. Complement-dependent cytotoxicity and antiproliferative activity were not observed for either antibody. Pr1E11 exhibited higher antitumor activity than AR47A6.4.2 in vivo.
  
  
  
  Our results suggest that high cell surface retention can result in potent ADCC activity in vivo. This observation could provide novel insight into how effectively screen for antibodies with strong in vivo antitumor activity.
authors: Kyowa Hakko Kirin Co., Ltd., Machida-shi, Japan masahiro.ikeda@kyowa-kirin.co.jp.
authors: Masahiro
authors: M
authors: Ikeda
authors: Department of Biomedical Engineering, Toyo University, Kawagoe, Japan.|Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Kazunori
authors: K
authors: Kato
authors: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Miki
authors: M
authors: Yamaguchi
authors: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Laboratory of Oncology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
authors: Hirofumi
authors: H
authors: Hamada
authors: Kyowa Hakko Kirin Co., Ltd., Machida-shi, Japan.
authors: Kazuyasu
authors: K
authors: Nakamura
authors: Kyowa Hakko Kirin Co., Ltd., Machida-shi, Japan.
authors: Yoshiyuki
authors: Y
authors: Sugimoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human
keywords: Antibody-dependent cellular cytotoxicity; TROP2; cell surface retention; monoclonal antibody; solid tumor