Monocyte-Derived Dendritic Cells from HLA-Matched Allogeneic Donors Showed Superiority To Induce Leukemic Cell-Specific T Cells in Comparison to Leukemic Cell-Derived Dendritic Cells or Monocyte-Derived Dendritic Cells from AML Patients.

Leukemic-dendritic cells (leukemic-DCs) have certain limitations, which include difficult generation in 30–40% of patients, and low levels of expression of several key molecules. To overcome these limitations, autologous mononocyte-derived DCs (autologous-DCs) from the patients can use as an alternative approach, but the DCs may have some defective functions. In this study, we investigated the feasibility of immunotherapy for AML using leukemic-cell specific cytotoxic T lymphocytes that were stimulated by allogeneic monocyte-derived DCs (allogeneic-DCs) pulsed with leukemic cell lysates in vitro. To generate autologous- or allogenic-DCs, CD14+cells isolated from mononuclear cells (MNCs) of the patients or of HLA-matched donors were cultured in the medium with GM-CSF and IL-4 for 6 days. Their maturation was induced by adding TNF-α, IL-1β, IL-6, and PGE₂ for 2 days, and then, leukemic cell lysates were pulsed. To generate leukemic-DCs, MNCs obtained from AML patients were cultured in the presence of GM-CSF, IL-4, and TNF-α for 8–12 days. The expressions of several key molecules on allogeneic-DCs were significantly higher than that on leukemic-DCs or autologous-DCs. Allogeneic-DCs exhibited a higher capacity to stimulate allogeneic CD3+ T cells compared to leukemic-DCs or autologous-DCs in allogeneic mixed lymphocyte reaction assay. Autologous CD3+ T cells stimulated by HLA-matched allogeneic-DCs pulsing with leukemic cell lysates showed more potent cytotoxic activities against autologous leukemic cells than those stimulated by leukemic-DCs or autologous-DCs. In addition, autologous-DC showed an intermediate level between leukemic-DCs and allogeneic-DCs in phenotypic expressions, allogeneic T-cell stimulatory capacities, or cytotoxic activities. In conclusion, these results suggest that monocyte derived-DCs from HLA-matched allogeneic donors can alternatively use to generate leukemic cell-specific cytotoxic T cells and to overcome the limitation of leukemic-DCs or autologous-DCs.