Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia

Aniruddha Choudhury, James L. Gajewski, Jan C. Liang, Uday Popat, David F. Claxton, Kay Oliver Kliche, Michael Andreeff, Richard E. Champlin

    Research output: Contribution to journalArticle

    280 Scopus citations

    Abstract

    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-α 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 leukemia 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, leukemia DCs displayed vigorous cytotoxic activity against CML cells but low reactivity to major histocompatibility 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.

    Original languageEnglish (US)
    Pages (from-to)1133-1142
    Number of pages10
    JournalBlood
    Volume89
    Issue number4
    DOIs
    StatePublished - Feb 15 1997

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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  • Cite this

    Choudhury, A., Gajewski, J. L., Liang, J. C., Popat, U., Claxton, D. F., Kliche, K. O., Andreeff, M., & Champlin, R. E. (1997). Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. Blood, 89(4), 1133-1142. https://doi.org/10.1182/blood.v89.4.1133