In:
Journal of Immunotherapy, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 5 ( 2019-06), p. 143-161
Abstract:
Strategies to stabilize remissions by specific elimination of residual acute myeloid leukemia (AML) blasts are needed. Leukemia-derived dendritic cell (DC leu /DC) generated from myeloid blasts improve antileukemic T-cell reactivity and install T-cell memory. Interferon (IFN)α-DC methods produce DC leu from chronic myeloid leukemia-patients (pts’) blood. Various INFα-containing versus other DC methods were studied to produce DC leu (evaluated by flowcytometry) from AML-pts’ blast-containing mononuclear (MNC) or whole blood (WB). After DC leu /DC stimulation in mixed lymphocyte cultures, T cells’ potential to gain antileukemic cytotoxicity was studied and correlated with different DC methods and DC leu /DC counts. (1) Generation of DC leu /DC: (a) “IFN-GIT” [containing granulocyte macrophage-colony stimulating factor (GM-CSF)+IFNα+ tumor necrosis factor (TNF)-α] produced DC successfully (≥10% DC, ≥5% DC leu /cells) from AML-MNC (WB) in 54 (56%), “MCM-Mimic” in 76 (75%), “Picibanil” in 83 (64%), and “Calcium-ionophore” in 42 (67%) of cases. Proportions of DC subtypes in MNC (WB) were comparable with all DC methods, (b) IFNα combinations containing only GM-CSF+IFNα or only IFNα showed low efficiency to produce DC leu /DC from MNC (WB) compared with “IFN-GIT.” (2) Antileukemic functionality: DC leu /DC-stimulated T cells showed improved leukemia cytotoxicity compared with blast cells or unprimed (“up”) T cells. The highest blast proliferation (=insufficient T cells) was seen with “IFN-GIT” DC-stimulated T cells. Probability to respond to immunotherapy or to obtain blast lysis of DC-stimulated T cells correlated with high proportions of DC leu /DC after DC culture, independent of DC-generating methods. (3) Cytokine release profiles: levels of interleukin-6, IFN-γ, and interleukin-2 were significantly lower in DC culture supernatants (from MNC/WB) with “IFN-GIT” compared with “MCM,” “Pici,” and “Ca” DC supernatants. Our data show that (1) WB culture simulates AML-pts’ in vivo situation, (2) DC generation is possible from AML-MNC (WB) with IFNα-containing and other DC methods, (3) successful IFNα-DC generation needs GM-CSF+IFNα+TNF-α (IFN-GIT); however, “IFN-GIT” produces less DC leu /DC compared with other (non-IFNα) DC methods, (4) T cells stimulated with “IFN-GIT”-produced DC leu /DC yielded comparable antileukemic cytotoxicity; however, in cases without achieved blast lysis, an increased blast proliferation was observed.
Type of Medium:
Online Resource
ISSN:
1524-9557
DOI:
10.1097/CJI.0000000000000266
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2048797-6
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