Efficient induction of specific cytotoxic T lymphocytes to tumor rejection peptide using functional matured 2 day-cultured dendritic cells derived from human monocytes.
Dendritic cells (DCs) are powerful antigen-presenting cells (APCs), that have so far been applied for cancer specific immunotherapy. Recent results suggest that matured DCs derived from human monocytes have a significant impact on the outcome of vaccination. The conventional generation of mature DCs from human monocytes in vitro has been reported to require 5 days for differentiation with granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and 2 days for stimulation. We herein report a new strategy for the functional maturation of monocyte-derived DCs within only 2 days of in vitro culture and the induction of specific cytotoxic T lymphocytes (CTLs) to tumor rejection peptide. The monocytes were incubated for 1 day with GM-CSF and IL-4, followed by activation with a bacterial product, OK-432 and prostaglandin E2 (PGE2) for another 1 day (rapid DC). Rapid DC expressed mature DC surface markers as well as chemokine receptor 7 and secreted Th1-type cytokines. The DCs generated in this study mobilized Ca2+ in response to CCL21/6Ckine and SDF-1, but only marginally did so to Mip-1alpha. Moreover, when rapid DC were compared with mature conventional 7-day DCs, they were equally potent in inducing specific CTLs in vitro. These results indicate that the rapid DC is as effective as the monocyte-derived conventional DCs. The rapid DC would be a potentially useful new cancer-specific immunotherapy.
Tanaka
Fumiaki
F
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan.
Yamaguchi
Hiroshi
H
Haraguchi
Naotsugu
N
Mashino
Kohjiro
K
Ohta
Mitsuhiko
M
Inoue
Hiroshi
H
Mori
Masaki
M
D000951:Antigens, Neoplasm / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D015232:Dinoprostone / Q000494:pharmacology; D015234:HLA-A Antigens / Q000494:pharmacology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D009363:Neoplasm Proteins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010844:Picibanil / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D000951:Antigens, Neoplasm; C515478:CCL21 protein, human; C515255:CXCL12 protein, human; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D015234:HLA-A Antigens; C037164:HLA-A28 antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D018664:Interleukin-12; D010844:Picibanil; D007371:Interferon-gamma; D015232:Dinoprostone; D002118:Calcium