Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential cellular vaccine for acute myeloid leukaemia.
We assessed the potential of tumour cell/dendritic cell fusion hybrids to generate in vitro anti-leukaemic T-cell responses following co-culture with autologous remission lymphocytes in six patients with acute myeloid leukaemia (AML). Comparison was made to anti-leukaemic responses induced by mature dendritic cells (mDC) co-cultured with autologous, irradiated myeloid blasts. Fusion hybrids induced anti-leukaemic T-cell immune responses in three of six patients. Tumour-pulsed mDC induced T-cellular responses in two other patients. Only one of six patients remission lymphocytes failed to develop leukaemia-directed immune responses following stimulation with either construct. Anti-proliferative properties of fusion hybrids against allogeneic lymphocytes were observed in mixed lymphocyte-leukaemia reactions and were found not to be specific to the cell fusion partners and did not prevent the ability of AML-mDC heterokaryons to induce autologous anti-leukaemic cytotoxicity. We conclude that tumour cell/dendritic cell fusion hybrids hold promise as a cellular vaccine for AML.
Klammer
M
M
University of Edinburgh-Leukaemia Research Fund, John Hughes Bennett Laboratory, Western General Hospital, Edinburgh EH4 2XU, UK. matt@klammermatt.demon.co.uk
Waterfall
M
M
Samuel
K
K
Turner
M L
ML
Roddie
P H
PH
D000208:Acute Disease; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology*; D002459:Cell Fusion; D049109:Cell Proliferation; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines