title: Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope.
abstract: TROP-2 is a type Ⅰ transmembrane glycoprotein that is highly expressed in various epithelial cancer cells, and its increased expression correlates with poor prognosis. Although several anti-TROP-2 antibodies have been described, they were found unsuitable for antitumor therapy use in vivo as naked antibodies. In this study, we established a novel anti-TROP-2 antibody, designated Pr1E11, from mice immunized with primary prostate cancer cells. Antibody screening was based on the infection activity of Adv-LacZ-FZ33, which displays an immunoglobulin G binding domain in the adenoviral fiber protein. We found that Pr1E11 specifically binds to TROP-2 with high affinity and recognizes diverse epithelial cancer cell lines and primary pancreatic cancer tissues. Epitope analysis using TROP-2 deletion mutants revealed that binding site of Pr1E11 is a cysteine-rich domain, a unique epitope compared with other available anti-TROP-2 antibodies. In addition, Pr1E11 exhibited low internalization activity, which may make it suitable for naked antibody therapeutics. Our results suggest that Pr1E11 may stimulate different biological activities from other anti-TROP-2 antibodies based on its unique binding epitope, and is a potential candidate for naked antibody therapeutics for various epithelial cancer treatments.
authors.affiliation: Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan. Electronic address: masahiro.ikeda@kyowa-kirin.co.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8556, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Biomedical Engineering, Toyo University, Kawagoe, Saitama 350-8585, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cell Biological Science, Faculty of Advanced Life Science, Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Sagano
authors.initials: S
authors.lastname: Shiina
authors.affiliation: Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ichikawa-Ando
authors.affiliation: Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Misaka
authors.affiliation: Fuji Research Park, Kyowa Hakko Kirin Co., Ltd., Nagaizumi-cho, Sunto-gun, Shizuoka 441-8731, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Myojo
authors.affiliation: Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8556, Japan; Laboratory of Oncology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011467:Prostate / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology*; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000939:Epitopes; C499380:TACSTD2 protein, human
keywords: Antibody; Epitope; Internalization; Modified adenovirus vector; TROP-2