Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL

Leukemia. 2004 Nov;18(11):1810-5. doi: 10.1038/sj.leu.2403517.


B cell chronic lymphocytic leukemia (B-CLL) is a chronic leukemia manifested by increased numbers of B cells in circulation. The slow, smouldering nature of the disease in a significant proportion of the cases makes it an ideal target for immunotherapy. Dendritic cell (DC)-based immunotherapy is emerging as an exciting modality with significant clinical potential. In this study, three strategies for delivering antigens to DC, namely apoptotic bodies (Apo-DC), tumor lysates, and tumor RNA were studied in an autologous setting. In all six CLL patients, Apo-DC induced higher HLA-restricted, T cell responses than DC pulsed with tumor lysate or RNA. Real-time PCR confirmed higher expression of genes for IL-2 and IFN-gamma in T cells stimulated with Apo-DC. Concurrently, no IL-10 and low IL-4 responses indicated that the immune response was primarily of the Th1 type. Enzyme-linked immunospot assay revealed high IFN-gamma secretion by T cells when Apo-DC was used to stimulate autologous T cells in all patients. Our data suggest that cellular vaccines with DC loaded with apoptotic bodies may be a suitable approach for immunotherapy of B-CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Neoplasm / immunology
  • Apoptosis / immunology*
  • Cell Extracts / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunophenotyping
  • Immunotherapy*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Cell Extracts
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Interleukin-2
  • RNA, Messenger
  • RNA, Neoplasm
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma