Anti-glypican-1 antibody–drug conjugate is a potential therapy against pancreatic cancer

Takahiko Nishigaki, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Tomoharu Ohkawara, Hisashi Hara, Takahito Sugase, Toru Otsuru, Yurina Saito, Shigehiro Tsujii, Taisei Nomura, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Kiyokazu Nakajima, Hidetoshi Eguchi, Makoto Yamasaki, Masaki Mori, Yuichiro DokiTetsuji Naka

Research output: Contribution to journalArticle

Abstract

Background: Pancreatic cancer (PDAC) is the most lethal malignancy. New treatment options for it are urgently required. The aim was to develop an antibody–drug conjugate (ADC) targeting glypican-1 (GPC-1) as a new therapy for PDAC. Methods: We evaluated GPC-1 expression in resected PDAC specimens and PDAC cell lines. We then measured the antitumour effect of anti-GPC-1 monoclonal antibody conjugated with the cytotoxic agent monomethyl auristatin F (MMAF) in vitro and in vivo. Results: GPC-1 was overexpressed in most primary PDAC cells and tissues. The PDAC cell lines BxPC-3 and T3M-4 strongly expressed GPC-1 relative to SUIT-2 cells. Compared with control ADC, GPC-1-ADC showed a potent antitumour effect against BxPC-3 and T3M-4, but little activity against SUIT-2 cells. In the xenograft and patient-derived tumour models, GPC-1-ADC significantly and potently inhibited tumour growth in a dose-dependent manner. GPC-1-ADC-mediated G2/M-phase cell cycle arrest was detected in the tumour tissues of GPC-1-ADC-treated mice relative to those of control-ADC-treated mice. Conclusions: GPC-1-ADC showed significant tumour growth inhibition against GPC-1-positive pancreatic cell lines and patient-derived, GPC-1-positive pancreatic cancer tissues. Our preclinical data demonstrated that targeting GPC-1 with ADC is a promising therapy for patients with GPC-1-positive pancreatic cancer.

Original languageEnglish
Pages (from-to)1333-1341
Number of pages9
JournalBritish journal of cancer
Volume122
Issue number9
DOIs
Publication statusPublished - Apr 28 2020

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Nishigaki, T., Takahashi, T., Serada, S., Fujimoto, M., Ohkawara, T., Hara, H., ... Naka, T. (2020). Anti-glypican-1 antibody–drug conjugate is a potential therapy against pancreatic cancer. British journal of cancer, 122(9), 1333-1341. https://doi.org/10.1038/s41416-020-0781-2