Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL

Leukemia. 2003 May;17(5):894-9. doi: 10.1038/sj.leu.2402913.

Abstract

Dendritic cells (DC) are professional (specialised) antigen-presenting cells that can capture antigen from apoptotic tumour cells and induce MHC class I- and II-restricted responses. Also, DC fused with tumour cells may be effective for immune response induction. Both cell preparations may be considered as vaccine candidates in a therapeutic approach. We examined autologous T-cell activation by DC that had endocytosed leukaemic B-cell apoptotic bodies (Apo-DC) and compared it to the T-cell stimulatory capacity of DC that were fused with tumour cells. Following incubation, 22.6+/-6.2 (mean+/-s.e.m.) of DC had endocytosed leukaemic cells, while the frequency of DC-leukaemic cell hybrids was 10.5+/-2.6%. Apo-DC and hybrid cells both demonstrated the ability to stimulate a tumour-specific T-cell immune response in vitro. A T-cell proliferation response was also observed in four out of five CLL patients when using Apo-DC. However, fusion hybrids lacked the ability to elicit a proliferative response. Apo-DC also induced an IFN-gamma response, as did hybrid cells. The cytokine response induced by Apo-DC was significantly higher than that induced by fusion (P<0.05). This study shows that endocytosed apoptotic tumour cells induced a significantly stronger T-cell response than DC hybrids; and as such should be a better candidate for vaccine production.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen Presentation
  • Antigens, CD / metabolism
  • Apoptosis*
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Cell Division
  • Cell Fusion
  • Chimera
  • Dendritic Cells / immunology*
  • Endocytosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunophenotyping
  • Immunotherapy
  • Interferon-gamma / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Histocompatibility Antigens Class I
  • Interferon-gamma