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.