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- Title
Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer.
- Authors
Nishigaki, Takahiko; Takahashi, Tsuyoshi; Serada, Satoshi; Fujimoto, Minoru; Ohkawara, Tomoharu; Hara, Hisashi; Sugase, Takahito; Otsuru, Toru; Saito, Yurina; Tsujii, Shigehiro; Nomura, Taisei; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Nakajima, Kiyokazu; Eguchi, Hidetoshi; Yamasaki, Makoto; Mori, Masaki; Doki, Yuichiro
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
British Journal of Cancer, 2020, Vol 122, Issue 9, p1333
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-020-0781-2