In Vivo Administration of Recombinant Human Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination
Shigetaka Shimodaira,
Ryu Yanagisawa,
Terutsugu Koya,
Koichi Hirabayashi,
Yumiko Higuchi,
Takuya Sakamoto,
Misa Togi,
Tomohisa Kato,
Takashi Kobayashi,
Tomonobu Koizumi,
Shigeo Koido,
Haruo Sugiyama
Affiliations
Shigetaka Shimodaira
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan
Ryu Yanagisawa
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 390-8621, Japan
Terutsugu Koya
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan
Koichi Hirabayashi
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 390-8621, Japan
Yumiko Higuchi
Department of Clinical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Takuya Sakamoto
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan
Misa Togi
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan
Tomohisa Kato
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan
Takashi Kobayashi
Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 390-8621, Japan
Tomonobu Koizumi
Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 390-8621, Japan
Shigeo Koido
Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Kashiwa, Chiba 277-8567, Japan
Haruo Sugiyama
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
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.
