論文 - 詳細
| RRC ID | 58802 |
|---|---|
| 著者 | Nishigaki T, Takahashi T, Serada S, Fujimoto M, Ohkawara T, Hara H, Sugase T, Otsuru T, Saito Y, Tsujii S, Nomura T, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Nakajima K, Eguchi H, Yamasaki M, Mori M, Doki Y, Naka T. |
| タイトル | Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer. |
| ジャーナル | Br J Cancer |
| 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. |
| 巻・号 | 122(9) |
| ページ | 1333-1341 |
| 公開日 | 2020-4-1 |
| DOI | 10.1038/s41416-020-0781-2 |
| PII | 10.1038/s41416-020-0781-2 |
| PMID | 32152502 |
| PMC | PMC7189381 |
| MeSH | Animals Antibodies, Anti-Idiotypic / pharmacology* Antibodies, Monoclonal / pharmacology Cell Line, Tumor Cell Proliferation / drug effects Glypicans / genetics* Humans Immunoconjugates / pharmacology* Mice Oligopeptides / pharmacology Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / genetics Pancreatic Neoplasms / pathology Xenograft Model Antitumor Assays |
| IF | 5.791 |
| 引用数 | 1 |
| リソース情報 | |
| ヒト・動物細胞 | T3M-4(RCB1021) |