Dendritic cells fused with core binding factor-beta positive acute myeloid leukaemia blast cells induce activation of cytotoxic lymphocytes.
Several reports have described various strategies of dendritic cell (DC) vaccination to induce specific T-cell responses in patients with acute myeloid leukaemia (AML). About 50-60% of AML cases blasts have chromosomal abnormalities, such as inv(16) or t(8,21), which could encode for leukaemia-specific antigenic peptide sequences, possibly presented in the context of self-major histocompatibility complex (MHC) molecules. As the co-culture of AML blasts with T lymphocytes seldom resulted in T-cell stimulation, we fused AML blasts with autologous DC to enhance this effect. The fusion cells expressed MHC class I and II, CD40, B7-1, B7-2, CD209 and several adhesion molecules. In a mixed lymphocyte hybrid reaction, the fusion cells induced the proliferation of autologous T cells. Moreover, in the special case of fusion cells established from AML blasts with the chromosomal abnormality inv(16), the autologous T lymphocytes could be primed to induce cytotoxicity against up to 70% autologous AML blasts in a effector:target ratio of 20:1. Blocking assays demonstrated that the lysis was chiefly mediated by CD8(+), CCR7(-) T lymphocytes, which could be further expanded in the form of effector memory CD8(+) T cells by repeated co-cultures with the autologous fusion cells.
Banat
G-Andre
GA
Department of Haematology and Oncology, Medical Centre University of Giessen, Giessen, Germany. a.banat@innere.med.uni-giessen.de
Usluoglu
Nurguel
N
Hoeck
Marianne
M
Ihlow
Kerstin
K
Hoppmann
Sabine
S
Pralle
Hans
H
D000208:Acute Disease; D002455:Cell Division / Q000276:immunology; D002459:Cell Fusion; D002869:Chromosome Aberrations; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004268:DNA-Binding Proteins / Q000032:analysis*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007951:Leukemia, Myeloid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009363:Neoplasm Proteins / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000032:analysis*
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors