Abstract
Our previous data have shown a significantly higher tumor response to anti-CD3/anti-Pgp bispecific diabody-mediated immunotherapy for P-glycoprotein (Pgp)-overexpressing K562/A02 cells, but a rapid tumor relapse occurred at 1 week after therapy. In an attempt to overcome tumor recurrence, we supplemented the previous therapy with extracellular domain of human 4-1BBL (ex4-1BBL) to regulate the activation of peripheral blood lymphocyte (PBL). As a result, this combination showed enhanced cytotoxicity in vitro and eradicated the multidrug-resistant xenografts of K562/A02 in nude mice. Furthermore, no tumor recurrence was observed within 100 days after the first treatment. Therefore, when used as an adjuvant, ex4-1BBL may improve the outcome of PBL-based immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-1BB Ligand / biosynthesis
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4-1BB Ligand / genetics
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4-1BB Ligand / pharmacology*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / immunology*
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Animals
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Antibodies, Bispecific / immunology
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Antibodies, Bispecific / therapeutic use*
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CD3 Complex / immunology*
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Cell Proliferation / drug effects
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Drug Resistance, Neoplasm
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Female
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Humans
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Immunotherapy / methods*
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Interleukin-2 / immunology
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Jurkat Cells
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K562 Cells
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Leukemia / immunology
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Leukemia / therapy*
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Lymphocytes / drug effects
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Lymphocytes / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Protein Structure, Tertiary
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Random Allocation
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Specific Pathogen-Free Organisms
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
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Xenograft Model Antitumor Assays
Substances
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4-1BB Ligand
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibodies, Bispecific
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CD3 Complex
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Interleukin-2
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TNFRSF9 protein, human
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Tumor Necrosis Factor Receptor Superfamily, Member 9