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

279 Citations (Scopus)

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
StatePublished - Feb 15 1997
Externally publishedYes

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Philadelphia Chromosome
T-cells
Cytotoxicity
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosomes
Dendritic Cells
T-Lymphocytes
Leukemia
Antigen-Presenting Cells
Assays
Cells
Adoptive Immunotherapy
Lymphocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Major Histocompatibility Complex
Cell Nucleus
Fluorescence In Situ Hybridization
Cell culture
Bone Marrow Cells
Interleukin-4

ASJC Scopus subject areas

  • Hematology

Cite this

Choudhury, A., Gajewski, J. L., Liang, J. C., Popat, U., Claxton, D. F., Kliche, K. O., ... 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.

Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. / Choudhury, Aniruddha; Gajewski, James L.; Liang, Jan C.; Popat, Uday; Claxton, David F.; Kliche, Kay Oliver; Andreeff, Michael; Champlin, Richard E.

In: Blood, Vol. 89, No. 4, 15.02.1997, p. 1133-1142.

Research output: Contribution to journalArticle

Choudhury, A, Gajewski, JL, Liang, JC, Popat, U, Claxton, DF, Kliche, KO, Andreeff, M & Champlin, RE 1997, 'Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia', Blood, vol. 89, no. 4, pp. 1133-1142.
Choudhury, Aniruddha ; Gajewski, James L. ; Liang, Jan C. ; Popat, Uday ; Claxton, David F. ; Kliche, Kay Oliver ; Andreeff, Michael ; Champlin, Richard E. / Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. In: Blood. 1997 ; Vol. 89, No. 4. pp. 1133-1142.
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