Efficient induction of specific cytotoxic T lymphocytes to tumor rejection peptide using functional matured 2 day-cultured dendritic cells derived from human monocytes.

Abstract

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.

• Authors: Fumiaki Tanaka, Hiroshi Yamaguchi, Naotsugu Haraguchi, Kohjiro Mashino, Mitsuhiko Ohta, Hiroshi Inoue, Masaki Mori
• Journal: International journal of oncology (Int J Oncol) Vol. 29 Issue 5 Pg. 1263-8 (Nov 2006) ISSN: 1019-6439 [Print] Greece
• PMID: 17016660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• CCL21 protein, human
• CXCL12 protein, human
• Chemokine CCL21
• Chemokine CXCL12
• Chemokines, CC
• Chemokines, CXC
• Cytokines
• HLA-A Antigens
• HLA-A28 antigen
• MAGEA3 protein, human
• Neoplasm Proteins
• Peptides
• Interleukin-12
• Picibanil
• Interferon-gamma
• Dinoprostone
• Calcium

Topics

• Antigens, Neoplasm (pharmacology)
• Calcium (metabolism)
• Cell Culture Techniques (methods)
• Chemokine CCL21
• Chemokine CXCL12
• Chemokines, CC (pharmacology)
• Chemokines, CXC (pharmacology)
• Coculture Techniques
• Cytokines (metabolism)
• Dendritic Cells (cytology, immunology, transplantation)
• Dinoprostone (pharmacology)
• HLA-A Antigens (pharmacology)
• Humans
• Immunotherapy, Adoptive
• Interferon-gamma (metabolism)
• Interleukin-12 (metabolism)
• Monocytes (cytology, drug effects)
• Neoplasm Proteins (pharmacology)
• Peptides (pharmacology)
• Picibanil (pharmacology)
• T-Lymphocytes, Cytotoxic (immunology)
• Th1 Cells (immunology)