Shimodaira Shigetaka, Yanagisawa Ryu, Koya Terutsugu, Hirabayashi Koichi, Higuchi Yumiko, Sakamoto Takuya, Togi Misa, Kato Tomohisa, Kobayashi Takashi, Koizumi Tomonobu, Koido Shigeo, Sugiyama Haruo
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan.
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 390-8621, Japan.
Vaccines (Basel). 2019 Sep 19;7(3):120. doi: 10.3390/vaccines7030120.
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 CD11cCD80 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.
癌症免疫治疗领域最近取得的重大进展包括用肿瘤抗原相关肽脉冲树突状细胞(DC)对癌症患者进行疫苗接种。需要具有均匀、成熟和功能活性的DC疫苗来实现有效的获得性免疫;然而,自体单核细胞衍生DC的产量在每个患者中各不相同。在单采前16 - 18小时用低剂量重组人粒细胞集落刺激因子(rhG - CSF)进行预处理,收获的单核细胞增加了50%,CD11cCD80 DC/单采单核细胞的比例显著增加。基于使用四聚体分析的免疫监测,在用Wilms肿瘤1脉冲DC疫苗接种后,接受rhG - CSF治疗的患者中抗原特异性细胞毒性T淋巴细胞的检测率高于未接受治疗的患者。我们的研究首次报道,用低剂量rhG - CSF预处理的用于癌症免疫治疗的DC疫苗有望实现更高的获得性免疫原性。