Abstract
CD26 is a M(r) 110,000 surface glycoprotein with diverse functional properties, including having a potentially significant role in tumor development, and antibodies to CD26 mediate pleomorphic cellular functions. In this report, we show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces cell cycle arrest at the G1-S checkpoint, associated with enhanced p21 expression that is dependent on de novo protein synthesis. Furthermore, experiments with a severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment significantly enhances survival of tumor-bearing mice by inhibiting tumor formation. Our data therefore suggest that anti-CD26 treatment may have potential clinical use for CD26+ hematological malignancies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal / therapeutic use
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Antineoplastic Agents / pharmacology*
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Cell Division / drug effects
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / drug effects
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Cyclins / metabolism
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Dipeptidyl Peptidase 4 / immunology*
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Dipeptidyl Peptidase 4 / metabolism
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Dose-Response Relationship, Drug
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Female
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G1 Phase / drug effects
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Humans
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Lymphoma, Large-Cell, Anaplastic / mortality
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Lymphoma, Large-Cell, Anaplastic / pathology
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Lymphoma, Large-Cell, Anaplastic / prevention & control*
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Mice
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Mice, SCID
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Neoplasm Transplantation
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Proteins / drug effects
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Proteins / genetics
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Proteins / metabolism
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S Phase / drug effects
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Survival Rate
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Proteins
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Dipeptidyl Peptidase 4