Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses

We have previously reported that leukemic dendritic cells (DC) can be gener ated ex vivo from myelomonocytic precursors in chronic myelogenous leukemia . In this study we report the generation of DC from acute myelogenous leuke mia (AML) cells and their potent ability to stimulate leukemia-specific cyt olytic activity in autologous lymphocytes. DC were generated in vitro using granulocyte-macrophage colony-stimulating factor +interleukin-4 in combina tion with either tumor necrosis factor-alpha or CD40 ligand (CD40L). Cells from 19 AML patients with a variety of chromosomal abnormalities were studi ed for their ability to generate DC. In all but 1 case, cells with the morp hology, phenotypic characteristics, and T-cell stimulatory properties of DC could be generated. These cells expressed high levels of major histocompat ibility complex class I and class II antigens as well as the costimulatory molecules B7-2 and ICAM-1. In three cases these cells were determined to be of leukemic origin by fluorescence in situ hybridization for chromosomal a bnormalities or Western blotting for the inv(16) fusion gene product. Autol ogous lymphocytes cocultured with AML-derived DC (DC-AL) were able to lyse autologous leukemia targets, whereas little cytotoxicity was noted against autologous, normal cells obtained from the patients during remission. We co nclude that leukemia derived DC may be useful for immunotherapy of many AML patients. (C) 1999 by The American Society of Hematology.