PMID- 9028934 OWN - NLM STAT- MEDLINE DCOM- 19970317 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 89 IP - 4 DP - 1997 Feb 15 TI - Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. PG - 1133-42 AB - 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. FAU - Choudhury, A AU - Choudhury A AD - Department of Hematology and Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. FAU - Gajewski, J L AU - Gajewski JL FAU - Liang, J C AU - Liang JC FAU - Popat, U AU - Popat U FAU - Claxton, D F AU - Claxton DF FAU - Kliche, K O AU - Kliche KO FAU - Andreeff, M AU - Andreeff M FAU - Champlin, R E AU - Champlin RE LA - eng GR - CA49639/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Cytokines) RN - 0 (Interleukin-2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Cell Differentiation/drug effects MH - Coculture Techniques MH - Cytokines/*pharmacology MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*immunology/pathology MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - Immunophenotyping MH - Interleukin-2/pharmacology MH - Interleukin-4/pharmacology MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology MH - Leukemia, Myeloid, Chronic-Phase/*immunology MH - Lymphocyte Activation MH - Neoplastic Stem Cells/*immunology/pathology MH - T-Lymphocyte Subsets/drug effects/immunology MH - T-Lymphocytes, Cytotoxic/drug effects/*immunology MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/pharmacology MH - Tumor Stem Cell Assay EDAT- 1997/02/15 00:00 MHDA- 1997/02/15 00:01 CRDT- 1997/02/15 00:00 PHST- 1997/02/15 00:00 [pubmed] PHST- 1997/02/15 00:01 [medline] PHST- 1997/02/15 00:00 [entrez] AID - S0006-4971(20)58835-6 [pii] PST - ppublish SO - Blood. 1997 Feb 15;89(4):1133-42.