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Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 780-786
RAPID COMMUNICATION
Dendritic Cells Derived In Vitro From Acute Myelogenous Leukemia Cells
Stimulate Autologous, Antileukemic T-Cell Responses
A. Choudhury,
J.C. Liang,
E.K. Thomas,
L. Flores-Romo,
Q.S. Xie,
K. Agusala,
S. Sutaria,
I. Sinha,
R.E. Champlin, and
D.F. Claxton
From The University of Texas M.D. Anderson Cancer Center, Houston,
TX; and Immunex Corporation, Seattle, WA.
We have previously reported that leukemic dendritic cells (DC) can
be generated ex vivo from myelomonocytic precursors in chronic
myelogenous leukemia. In this study we report the generation of DC from
acute myelogenous leukemia (AML) cells and their potent ability to
stimulate leukemia-specific cytolytic activity in autologous lymphocytes. DC were generated in vitro using granulocyte-macrophage colony-stimulating factor +interleukin-4 in combination with either tumor necrosis factor- or CD40 ligand (CD40L). Cells from 19 AML
patients with a variety of chromosomal abnormalities were studied for
their ability to generate DC. In all but 1 case, cells with the
morphology, phenotypic characteristics, and T-cell stimulatory properties of DC could be generated. These cells expressed high levels
of major histocompatibility 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 abnormalities or
Western blotting for the inv(16) fusion gene product.
Autologous 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 conclude that leukemia derived DC may be useful
for immunotherapy of many AML patients.
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