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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Combination Immunotherapy with 4-1BB Activation and PD-1 Blockade Enhances Antitumor Efficacy in a Mouse Model of Subcutaneous Tumor
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Combination Immunotherapy with 4-1BB Activation and PD-1 Blockade Enhances Antitumor Efficacy in a Mouse Model of Subcutaneous Tumor

机译：4-1BB激活和PD-1阻断的联合免疫疗法增强了皮下肿瘤小鼠模型的抗肿瘤功效。

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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-I (PD-1) to blockade the immune checkpoint. Materials and Methods: Mice implanted with 1x10(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)-gamma(+) and CD8(+) IFN-gamma(+) 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.
机译：背景/目的：本研究的目的是通过使用抗4-1BB单克隆抗体（mAb）的组合将共信号平衡偏向阳性来建立有效的免疫疗法，也称为分化簇（CD） 137作为共同刺激效应物，并被编程为死亡I（PD-1）以阻断免疫检查点。材料和方法：植入1x10（5）CT26细胞的小鼠单独接受抗4-1BB mAb，单独抗PD-1 mAb或抗4-1BB mAb和抗PD-1 mAb的治疗。通过流式细胞仪分析免疫细胞群。通过免疫组织化学评估肿瘤浸润的T细胞。结果：联合治疗的小鼠具有最佳的抗肿瘤反应，可导致完全的肿瘤排斥。联合治疗组中CD4（+）干扰素（IFN）-γ（+）和CD8（+）IFN-γ（+）T细胞的数量明显更高。在联合治疗中，肿瘤浸润T细胞的数量显着增加。结论：靶向共信号分子的治疗策略在未来具有广阔的临床应用前景。

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