CpG oligodeoxynucleotides potentiate the antitumor activity of anti-BST2 antibody.
Numerous monoclonal antibodies (mAb) targeting tumor antigens have recently been developed. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) via effector cells such as tumor-infiltrating natural killer (NK) cells and macrophages are often involved in mediating the antitumor activity of mAb. CpG oligodeoxynucleotides (ODN) have a potent antitumor activity and are considered to increase tumor infiltration of NK cells and macrophages. Our group previously reported significant antitumor activity of anti-bone marrow stromal antigen 2 (BST2) mAb against BST2-positive endometrial cancer cells through ADCC. In this study, we evaluated the synergistic antitumor activity of combination therapy with anti-BST-2 mAb and CpG ODN using SCID mice and elucidated the mechanisms underlying this activity. Anti-BST2 mAb and CpG ODN monotherapy had a significant dose-dependent antitumor activity (P = 0.0135 and P = 0.0196, respectively). Combination therapy with anti-BST2 mAb and CpG ODN had a significant antitumor activity in SCID mice (P < 0.01), but not in NOG mice. FACS analysis revealed significantly increased numbers of NK cells and macrophages in tumors treated with a combination of anti-BST2 mAb and CpG ODN and with CpG ODN alone in SCID mice (P < 0.05 and P < 0.01, respectively). These results suggested that the combination therapy with anti-BST2 mAb and CpG ODN has a significant antitumor activity and induces tumor infiltration of NK cells and macrophages. Combination therapy with CpG ODN and anti-BST2 mAb or other antitumor mAb depending on ADCC may represent a new treatment option for cancer.
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.|Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Kosuke
K
Hiramatsu
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Satoshi
S
Serada
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Kouji
K
Kobiyama
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.|Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Satoshi
S
Nakagawa
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
Akiko
A
Morimoto
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
Shinya
S
Matsuzaki
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
Yutaka
Y
Ueda
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Minoru
M
Fujimoto
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
Kiyoshi
K
Yoshino
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Ken J
KJ
Ishii
Department of Obstetrics and Gynecology, Niigata University Medical School, Niigata, Japan.
Takayuki
T
Enomoto
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
Tadashi
T
Kimura
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Tetsuji
T
Naka
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays; D000074010:Bone Marrow Stromal Antigen 2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; D009838:Oligodeoxyribonucleotides; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C408982:CPG-oligonucleotide
Antitumor antibody; CpG oligodeoxynucleotides; bone marrow stromal antigen 2; macrophage; natural killer cell