In Vivo Administration of Recombinant Human Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination
In Vivo Administration of Recombinant Human Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination
复制标题
DOI：
10.3390/vaccines7030120
复制
发表时间：
2019-09-01
期刊：
影响因子：
7.8
通讯作者：
Sugiyama, Haruo
中科院分区：
文献类型：
--
作者：
Shimodaira, Shigetaka;Yanagisawa, Ryu;Sugiyama, Haruo
癌症免疫治疗的重大进展包括为癌症患者接种肿瘤抗原相关多肽冲击的树突状细胞(DC)。要获得有效的获得性免疫，需要具有同质、成熟和功能活性的DC疫苗；然而，每个患者自体单核细胞来源的DC的产量是不同的。采集前16~18h用小剂量重组人粒细胞集落刺激因子(rhG-CSF)预刺激，单核细胞获得率增加50%，CD11c(+)、CD80(+)DC/黏附性单核细胞比例显著升高。根据四聚体免疫监测结果显示，Wilms瘤1冲击DC疫苗接种后，接受rhG-CSF治疗的患者的抗原特异性细胞毒性T淋巴细胞的检出率高于未接受治疗的患者。我们的研究首次报道了以低剂量的人重组人粒细胞集落刺激因子启动的DC疫苗用于癌症免疫治疗有望获得更高的获得性免疫原性。
Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16-18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c(+)CD80(+) DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms' tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.