The generation of dendritic-like cells with increased allostimulatory function from acute myeloid leukemia cells of various FAB subclasses

To increase the immunogenicity of leukemic tells, attempts were made to gen erate dendritic-like antigen presenting cells (DC) from AML blasts from 14 patients with AML FAD classifications M0-M5. Leukemic cells were cultured i n the presence or absence of various cytokines including GM-CSF, SCF, TNF-a lpha, IL-4, and gamma-interferon. Alter various intervals recovery of viabl e cells was measured and expression of CD80, CD86, CD40, CD54, CD58, and CD 11a was analyzed by flow cytometry. Functionally, DC derived from six AML s amples were tested in a mixed lymphocyte response (MLR) using HLA-DR mismat ched donor T cells as responder cells. Proliferation (5/14) or increased su rvival (7/14) of AML cells was observed in the presence of GM-CSF, SCF, and TNF-alpha. Only in the AML M2, M3, and M4 FAB subtypes proliferation was f ound. GM-CSF, SCF, and TNF-alpha induced morphologic changes typical fur DC and increased th expression of costimulatory and adhesion molecules. No si gnificant effect of IL-4 or gamma-interferon was observed. The day of maxim al expression of these molecules varied. In cases with minor upregulation o f CD80 or CD86, no further stimulation using CD40-L activation was observed . In the three cases tested, the DC-like cells retained the chromosomal abn ormalities present in the original AML cells. In five out of six casts test ed an increase in allostimulatory capacity was found at the day of maximal expression of costimulatory and adhesion molecules. In two patients a decre ase in stimulatory capacity was found at day 7 compared with dap 2 correlat ing with a decreased expression of these molecules. In conclusion, ARIL cel ls can be induced to increase their stimulatory capacity by upregulating co stimulatory and adhesion molecules. (C) American Society for Histocompatibi lity and Immunogenetics, 2000. Published by Elsevier Science Inc.