RT Journal Article SR Electronic T1 Combination Immunotherapy with 4-1BB Activation and PD-1 Blockade Enhances Antitumor Efficacy in a Mouse Model of Subcutaneous Tumor JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 129 OP 136 VO 35 IS 1 A1 YOSHITARO SHINDO A1 KIYOSHI YOSHIMURA A1 ATSUO KURAMASU A1 YUSAKU WATANABE A1 HIDEAKI ITO A1 TOMOKO KONDO A1 ATSUNORI OGA A1 HIROSHI ITO A1 SHIGEFUMI YOSHINO A1 SHOICHI HAZAMA A1 KOJI TAMADA A1 HIDEO YAGITA A1 MASAAKI OKA YR 2015 UL http://ar.iiarjournals.org/content/35/1/129.abstract AB 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 1×105 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.