In Vivo Administration of Recombinant Human Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination

体内注射重组人粒细胞集落刺激因子可增强基于树突状细胞的癌症疫苗的免疫效果

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作者:Shigetaka Shimodaira, Ryu Yanagisawa, Terutsugu Koya, Koichi Hirabayashi, Yumiko Higuchi, Takuya Sakamoto, Misa Togi, Tomohisa Kato Jr, Takashi Kobayashi, Tomonobu Koizumi, Shigeo Koido, Haruo Sugiyama

Abstract

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.

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