2. Academic Validation
  3. Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope

Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope

  • Biochem Biophys Res Commun. 2015 Mar 20;458(4):877-82. doi: 10.1016/j.bbrc.2015.02.051.
Masahiro Ikeda 1,  Miki Yamaguchi 2,  Kazunori Kato 3,  Kiminori Nakamura 4,  Sagano Shiina 5,  Takako Ichikawa-Ando 5,  Hirofumi Misaka 5,  Kensuke Myojo 6,  Kazuyasu Nakamura 5,  Yoshiyuki Sugimoto 5,  Hirofumi Hamada 7
Affiliations

Affiliations

  • 1 Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan. Electronic address: masahiro.ikeda@kyowa-kirin.co.jp.
  • 2 Department of Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8556, Japan.
  • 3 Department of Biomedical Engineering, Toyo University, Kawagoe, Saitama 350-8585, Japan.
  • 4 Department of Cell Biological Science, Faculty of Advanced Life Science, Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan.
  • 5 Tokyo Research Park, Kyowa Hakko Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
  • 6 Fuji Research Park, Kyowa Hakko Kirin Co., Ltd., Nagaizumi-cho, Sunto-gun, Shizuoka 441-8731, Japan.
  • 7 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.
PMID: 25701778 DOI: 10.1016/j.bbrc.2015.02.051
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.

Keywords

Antibody; Epitope; Internalization; Modified adenovirus vector; TROP-2.

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