Yoshitaro Shindo1, Kiyoshi Yoshimura2, Atsuo Kuramasu3, Yusaku Watanabe1, Hideaki Ito4, Tomoko Kondo4, Atsunori Oga4, Hiroshi Ito4, Shigefumi Yoshino1, Shoichi Hazama1, Koji Tamada5, Hideo Yagita6, Masaaki Oka1. 1. Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. 2. Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center in Tsukiji, National Cancer Center, Chuo-ku, Tokyo, Japan kyoshim6705@gmail.com. 3. Department of Molecular Pharmacology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. 4. Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. 5. Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. 6. Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Abstract
BACKGROUND/AIM: The purpose of the present study was to establish an effective immunotherapy by skewing the cosignal balance to be on the positive side by using the combination of monoclonal antibody (mAb) against 4-1BB also known as Cluster of Differentiation (CD) 137 as a co-stimulatory effector and to programmed death-1 (PD-1) to blockade the immune checkpoint. MATERIALS AND METHODS: Mice implanted with 1×10(5) CT26 cells were treated with anti 4-1BB mAb alone, anti PD-1 mAb alone, or both anti 4-1BB mAb and anti PD-1 mAb. Immune cell populations were analyzed by flow cytometry. Tumor-infiltrating T-cells were evaluated by immunohistochemistry. RESULTS: Mice treated with the combination therapy had the best antitumor response that resulted in complete tumor rejection. The numbers of CD4(+) interferon (IFN)-γ(+) and CD8(+) IFN-γ(+) T-cells were significantly higher in the combination group. The number of tumor-infiltrating T-cells was significantly increased in the combination therapy. CONCLUSION: The therapeutic strategy of targeting co-signal molecules has promising clinical applications in the future. Copyright
BACKGROUND/AIM: The purpose of the present study was to establish an effective immunotherapy by skewing the cosignal balance to be on the positive side by using the combination of monoclonal antibody (mAb) against 4-1BB also known as Cluster of Differentiation (CD) 137 as a co-stimulatory effector and to programmed death-1 (PD-1) to blockade the immune checkpoint. MATERIALS AND METHODS:Mice implanted with 1×10(5) CT26 cells were treated with anti 4-1BB mAb alone, anti PD-1 mAb alone, or both anti 4-1BB mAb and anti PD-1 mAb. Immune cell populations were analyzed by flow cytometry. Tumor-infiltrating T-cells were evaluated by immunohistochemistry. RESULTS:Mice treated with the combination therapy had the best antitumor response that resulted in complete tumor rejection. The numbers of CD4(+) interferon (IFN)-γ(+) and CD8(+) IFN-γ(+) T-cells were significantly higher in the combination group. The number of tumor-infiltrating T-cells was significantly increased in the combination therapy. CONCLUSION: The therapeutic strategy of targeting co-signal molecules has promising clinical applications in the future. Copyright