論文 - 詳細
| RRC ID | 75755 |
|---|---|
| 著者 | Saito Y, Takahashi T, Hiramatsu K, Serada S, Fujimoto M, Ohkawara T, Sugase T, Nishigaki T, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Nakajima K, Yamasaki M, Ishii KJ, Eguchi H, Doki Y, Naka T. |
| タイトル | Nano-particulate Toll-like Receptor 9 Agonist Potentiates the Antitumor Activity of Anti-Glypican-1 Antibody. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Monoclonal antibodies (mAbs) that target tumor antigens have recently been developed. Their antitumor activity is mainly achieved through antibody-dependent cellular cytotoxicity (ADCC) via effector cells such as tumor-infiltrated macrophages and natural killer (NK) cells. CpG oligodeoxynucleotides (ODNs) have potent antitumor activity and are considered to increase the tumor infiltration of macrophages and NK cells; however, a completely solubilized novel CpG-schizophyllan (SPG) complex, K3-SPG, displays more potent antitumor activity. We recently reported the significant antitumor activity of anti-glypican-1 (GPC1) mAb against GPC1-positive esophageal squamous cell carcinoma (ESCC) via ADCC. The aim of this study was to evaluate the potential synergistic antitumor activity of anti-GPC1 mAb and K3-SPG and elucidate the underlying mechanisms using a xenograft model of GPC1-positive human ESCC cells. MATERIALS AND METHODS:The established human esophageal cancer cell line TE14 was subcutaneously injected into SCID mice. Xenograft mice were treated with anti-GPC1 mAb, K3-SPG, or their combination. Antitumor activity was evaluated by measuring the tumor volume. For FACS analysis, agents were administrated, and tumors were resected 1 day after the final treatment. RESULTS:Anti-GPC1 mAb or K3-SPG monotherapy showed dose-dependent antitumor activity, and combination therapy with anti-GPC1 mAb and K3-SPG showed antitumor activity (p=0.0859). Flow cytometry revealed significantly increased numbers of macrophages (p=0.0133) and of the ratio of activated NK cells/total NK cells (p=0.0058) following K3-SPG or combination therapy. CONCLUSION:Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC. |
| 巻・号 | 43(6) |
| ページ | 2425-2432 |
| 公開日 | 2023-6-1 |
| DOI | 10.21873/anticanres.16410 |
| PII | 43/6/2425 |
| PMID | 37247902 |
| MeSH | Adjuvants, Immunologic Animals Antibodies, Monoclonal / pharmacology Antibody-Dependent Cell Cytotoxicity Cell Line, Tumor Esophageal Neoplasms* / drug therapy Esophageal Squamous Cell Carcinoma* Glypicans Humans Mice Mice, SCID Toll-Like Receptor 9 |
| IF | 1.994 |
| リソース情報 | |
| ヒト・動物細胞 | TE-14(RCB2101) |