Dendritic cells fused with core binding factor-beta positive acute myeloid leukaemia blast cells induce activation of cytotoxic lymphocytes

Br J Haematol. 2004 Aug;126(4):593-601. doi: 10.1111/j.1365-2141.2004.05087.x.

Abstract

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.

MeSH terms

  • Acute Disease
  • Cell Division / immunology
  • Cell Fusion
  • Chromosome Aberrations
  • Coculture Techniques
  • Cytotoxicity, Immunologic / immunology
  • DNA-Binding Proteins / analysis*
  • Dendritic Cells / immunology*
  • Humans
  • Immunologic Memory / immunology
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / immunology*
  • Leukemia, Myeloid / metabolism
  • Lymphocyte Activation / immunology
  • Neoplasm Proteins / analysis*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transcription Factor AP-2
  • Transcription Factors / analysis*

Substances

  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Transcription Factor AP-2
  • Transcription Factors