Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Antibodies, Monoclonal / pharmacology
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Antigens, Neoplasm / immunology
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Apoptosis / immunology*
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Cell Extracts / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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Female
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Humans
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Immunophenotyping
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Immunotherapy*
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Interleukin-4 / genetics
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Interleukin-4 / metabolism
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Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
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Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
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Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
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Male
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / immunology*
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / immunology*
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T-Lymphocytes, Cytotoxic / immunology
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Th1 Cells
Substances
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Antibodies, Monoclonal
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Antigens, Neoplasm
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Cell Extracts
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Interleukin-2
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RNA, Messenger
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RNA, Neoplasm
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Interleukin-10
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Interleukin-4
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Interferon-gamma