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Use of leukemic dendritic cells for the generation of antileukemic cellular
cytotoxicity against Philadelphia chromosome-positive chronic myelogenous
leukemia
A Choudhury, JL Gajewski, JC Liang, U Popat, DF Claxton, KO Kliche, M Andreeff and RE Champlin
Department of Hematology and Laboratory Medicine, University of Texas M.D.
Anderson Cancer Center, Houston 77030, USA.
The success of adoptive immunotherapy for the treatment of leukemia depends
on the generation of T cells that can specifically react with malignant
cells. Dendritic cells (DCs) are important antigen-presenting cells in the
development of antileukemic T-cell responses. In this study, we generated
DCs from peripheral blood cells of patients with chronic myelogenous
leukemia (CML). CML cells incubated concurrently with
granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor
necrosis factor-alpha in vitro developed morphologic and phenotypic
characteristics of DCs. Fluorescence in situ hybridization showed the
presence of t(9;22) in the nuclei of these cells, indicating that they were
leukemic in origin. These cells were potent stimulators of lymphocyte
proliferation in specific in vitro assays for DC function. Autologous T
cells stimulated with in vitro-generated, leukemic DCs displayed vigorous
cytotoxic activity against CML cells but low reactivity to major
histocompatability complex-matched normal bone marrow cells. Cytotoxic
activity against CML targets was fourfold to sixfold higher using
DC-stimulated autologous T cells than with autologous T cells expanded by
culture with interleukin-2 alone. DC- stimulated T cells also inhibited
growth of CML clonogenic precursors in colony-forming assays in vitro.
These results suggest that cytokine- driven in vitro differentiation of CML
cells results in generation of DCs with potent T-cell stimulatory function.
In vitro-generated DCs can be effectively used as antigen-presenting cells
for the ex vivo expansion of antileukemic T cells.
Volume 89,
Issue 4,
pp. 1133-1142,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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