Nano-particulate Toll-like Receptor 9 Agonist Potentiates the Antitumor Activity of Anti-Glypican-1 Antibody.

Animals Humans Mice Adjuvants, Immunologic Antibodies, Monoclonal / pharmacology Antibody-Dependent Cell Cytotoxicity Cell Line, Tumor Esophageal Neoplasms / drug therapy Esophageal Squamous Cell Carcinoma Glypicans Mice, SCID Toll-Like Receptor 9 / agonists
Antitumor antibody CpG oligodeoxy-nucleotides glypican 1 macrophage natural killer cell

Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Jun 2023
Historique:
received: 05 04 2023
revised: 16 04 2023
accepted: 18 04 2023
medline: 31 5 2023
pubmed: 30 5 2023
entrez: 29 5 2023
Statut: ppublish

Résumé

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. 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. 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. Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
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 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 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 CONCLUSIONS
Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC.

Identifiants

DOI: 10.21873/anticanres.16410 PMID: 37247902
pubmed: 37247902
pii: 43/6/2425
doi: 10.21873/anticanres.16410
doi:

Substances chimiques

Adjuvants, Immunologic 0
Antibodies, Monoclonal 0
Glypicans 0
K3-SPG 0
Toll-Like Receptor 9 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2425-2432

Informations de copyright

Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Yurina Saito (Y)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.

Tsuyoshi Takahashi (T)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan; ttakahashi2@gesurg.med.osaka-u.ac.jp.

Kosuke Hiramatsu (K)

Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.

Satoshi Serada (S)

Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Institute for Biomedical Scienwces Molecular Pathophysiology, Iwate Medical University, Shiwa-gun, Japan.

Minoru Fujimoto (M)

Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Division of Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University, Shiwa-gun, Japan.

Tomoharu Ohkawara (T)

Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Division of Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University, Shiwa-gun, Japan.

Takahito Sugase (T)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Takahiko Nishigaki (T)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.

Koji Tanaka (K)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Yasuhiro Miyazaki (Y)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Tomoki Makino (T)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Yukinori Kurokawa (Y)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Kiyokazu Nakajima (K)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Makoto Yamasaki (M)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Ken J Ishii (KJ)

Laboratory of Mockup Vaccine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki, Japan.
Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Hidetoshi Eguchi (H)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Yuichiro Doki (Y)

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Tetsuji Naka (T)

Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan; tnaka@iwate-med.ac.jp.
Institute for Biomedical Scienwces Molecular Pathophysiology, Iwate Medical University, Shiwa-gun, Japan.
Division of Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University, Shiwa-gun, Japan.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Nano-particulate Toll-like Receptor 9 Agonist...
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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Nano-particulate Toll-like Receptor 9 Agonist...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Adjuvants immunologiques › Nano-particulate Toll-like Receptor 9 Agonist...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Nano-particulate Toll-like Receptor 9 Agonist...
questionsmedicales.fr › Phénomènes du système immunitaire › Cytotoxicité immunologique › Cytotoxicité à médiation cellulaire dépendante des anticorps › Nano-particulate Toll-like Receptor 9 Agonist...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › Glypicanes › Nano-particulate Toll-like Receptor 9 Agonist...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur-9 de type Toll-like › Nano-particulate Toll-like Receptor 9 Agonist...