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 antigenpresenting 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 E 2 (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 genereated in this study mobilized Ca2+ in response to CCL21/6Ckine and SDF-1, but only marginally did so to Mip-1α. 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.