Study On Dendritic Cells Generated In Vitro That Induce Anti-myeloid Leukemia Immune Response

Dendritic cells (DCs) are a specialized system of antigen-presenting cells. Only can DCs stimulate and activate naive T cells and play an important role in the development of anti-tumor immune response. To explore immunotherapy of (acute and chronic) myeloid leukemia (AML and CML), this study investigated the possibility of DC-based vaccine for the treatment of myeloid leukemia.Results:1.CML BMMC from 14 patients with new diagnosed CML were cultured in vitro for 7 — 8 days with GM-CSF, IL-4 and TNF-a. The cell recovery ratio is 61.04% ± 34.18%. The cultured cells developed morphologic, phenotypic characteristics of DCs. CD1a expression was found in approximately 30% of cultured cells. Their stimulator index (SI) in mixed lymphocyte reaction was 4.22 ±0.50, more potent than BMMC from same patients (SI=2.58±0.53, P=0.010), which indicated DCs function. DCs were not cultured only in one patient having received hydroxyurea for 14 days.Autologous T cells stimulated with CML generated in vitro DCs displayed marked cytotoxic activity against autologous CML target cells (E/T 20:1, 48.46%±15.76%). The cytotoxic activity against autologous CML target cells was markedly higher using DC-stimulated autologous T cells than with autologous T cells stimulated with IL-2 alone (1.09%± 0.49%,P=0.016) . DC stimulated T cells had same cytotoxic activity against K562 cells (15.06%± 6.06%) as did T cells stimulated with IL-2 alone (16.35%±10.03%, P=0.915). The phenotypes of T cells, whether DC used or IL-2 alone, were TCR78- CD3+, most of that were CD8+, accompanied with the increased activation marker (CD25 and HLA-DR) expression.2. AML BMMC from patients gained CR were cultured using SCF, GM-CSF plus IL-4, pulsed with AML cell lysates (WTL) at fifth day and TNF-a was added at sixth day. Following 7-8 days culture, cells developed morphologic, phenotypic characteristics of DCs. In non-pulsed and WTL pulsed groups, the cell recovery ratios were 63.24% ± 24.76% and 66.72% ± 26.35%, respectively. CD1a expression was found in...