Abstract
CD40-CD40-ligand (CD154) interactions play a critical role in immune activation. Using replication defective adenovirus encoding mouse CD154 (Ad-CD154), we modified human chronic lymphocytic leukemia B cells to express a functional ligand for CD40. This not only induces expression of immune accessory molecules on the infected cell, but also allows it to trans-activate noninfected bystander leukemia B cells. Also, factors that impair the antigen-presenting capacity of leukemia B cells are downmodulated. Ad-CD154- infected leukemia cells are highly effective stimulators in mixed lymphocyte reactions and can induce generation of cytotoxic T lymphocytes specific for autologous nonmodified leukemia cells. As such, Ad-CD154 can induce a host antileukemia response that may have therapeutic potential.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Antigen Presentation / genetics
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Antigens, CD / immunology
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B-Lymphocytes / immunology*
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CD40 Ligand
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Cytotoxicity Tests, Immunologic
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DNA, Complementary / genetics
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Flow Cytometry
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Gene Expression
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Gene Transfer Techniques
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Genetic Therapy / methods
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Genetic Vectors
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HeLa Cells
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Humans
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Immunity, Active / genetics
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
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Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
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Lymphocyte Culture Test, Mixed
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / immunology*
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Polymerase Chain Reaction
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Recombination, Genetic
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T-Lymphocytes, Cytotoxic / immunology
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Transcriptional Activation
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Tumor Cells, Cultured
Substances
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Antigens, CD
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DNA, Complementary
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Membrane Glycoproteins
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CD40 Ligand