The biological characteristics of dendritic cells derived in vitro from myelogeneous leukemia cells and healthy donor cells

Abstract

Successful adoptive immunotherapy for 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 antileukemia T-cell responses. Mononuclear cells (MNC) were isolated from peripheral blood or bone marrow of patients with chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML). After incubation with granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4, and tumor necrosis factor-alpha, MNC developed morphological characteristics of DCs in vitro, which were confirmed by phenotypic assay. Fluorescence in situ hybridization demonstrated the presence of fusion gene in the nuclei of representative CML or AML-M3 samples, indicating that the cells were leukemic in origin. IL-12 levels were significantly higher in AML-DCs and CML-DCs prestimulated with phorbol 12-myristate 13-acetate than in the corresponding leukemic cells, but were lower than that of healthy donors. These cells were potent stimulators of lymphocyte proliferation in specific in vitro assays for DC function. However, the stimulatory abilities of allogeneic T cells in a mixed lymphocyte reaction were impaired compared with those of mature DCs derived from healthy donors, although T-cell stimulatory effects were significantly increased in these differentiated leukemia-DCs. These results suggest that functional DCs may be derived from leukemic (AML, CML) blasts in a significant number of patients and may be capable of inducing leukemia-specific immune responses with potentially clinically beneficial effects.

Synergistic effect of Toll-like receptor 4 and 7/8 agonists is necessary to generate potent blast-derived dendritic cells in Acute Myeloid Leukemia

“…Our findings are consistent with some previous studies which reported that only in about 50-70% of AML patients could blasts be successfully differentiated into dendritic cells [25][26][27]39]. In optimal combination condition, the median recovery percentage of leukemic DC generation based on phenotypic criteria was 42% (range, 28-50%).…”

“…The most important advantage of generating AML-DC is the fact that all of the assumed leukemia-specific antigens would be presented by appropriate MHC molecules [38]. Recently, cocktails containing synthetic TLR agonists emerged as an attractive alternative for the induction of DC maturation [17][18][19]39]. Thus, we tried to optimize the generation and TLR agonist-dependent maturation of DCs derived from blasts of newly diagnosed AML patients.…”

Gastric cancer-derived heat shock protein-gp96 peptide complex enhances dendritic cell activation

“…DCs were cultured according to previous report[21-24]. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and suspended in 5-mL culture flasks with RPMI 1640 containing 10% fetal calf serum.…”

New insights into antigen specific immunotherapy for chronic myeloid leukemia

“…This is due to the PKC-induced differentiation associated with the down-regulation of BCR-ABL activity, which raises the possibility that CML-derived DC vaccines will be less effective in presenting leukemia-specific Ags [44]. The DC abnormalities in patients with CML may be abrogated by the proper in vitro stimulation of leukemic DCs [45-47]. However, in 2006, a phase I immunotherapy CML trial demonstrated that DC injections were well tolerated and safe, while no clinical responses was found [48].…”