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 SHINDO, YOSHITARO
A1 YOSHIMURA, KIYOSHI
A1 KURAMASU, ATSUO
A1 WATANABE, YUSAKU
A1 ITO, HIDEAKI
A1 KONDO, TOMOKO
A1 OGA, ATSUNORI
A1 ITO, HIROSHI
A1 YOSHINO, SHIGEFUMI
A1 HAZAMA, SHOICHI
A1 TAMADA, KOJI
A1 YAGITA, HIDEO
A1 OKA, MASAAKI
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.