Abstract
Because tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells and plays a critical role in tumor surveillance, its receptor is an attractive target for antibody-mediated tumor therapy. Here we report that a monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects against TRAIL-sensitive tumor cells in vivo by recruiting Fc receptor-expressing innate immune cells, with no apparent systemic toxicity. Administration of the agonistic anti-DR5 mAb also significantly inhibited experimental and spontaneous tumor metastases. Notably, the anti-DR5 mAb-mediated tumor rejection by innate immune cells efficiently evoked tumor-specific T cell immunity that could also eradicate TRAIL-resistant variants. These results suggested that the antibody-based therapy targeting DR5 is an efficient strategy not only to eliminate TRAIL-sensitive tumor cells, but also to induce tumor-specific T cell memory that affords a long-term protection from tumor recurrence.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine Transaminase / blood
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Animals
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Apoptosis Regulatory Proteins
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Aspartate Aminotransferases / blood
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Immunity, Cellular / immunology
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Immunotherapy / methods
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Mammary Neoplasms, Animal / immunology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Mice
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Mice, Inbred BALB C
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Mice, SCID
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Receptors, Fc / immunology
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / immunology*
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T-Lymphocytes / immunology*
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / deficiency
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Apoptosis Regulatory Proteins
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Membrane Glycoproteins
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Receptors, Fc
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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TNF-Related Apoptosis-Inducing Ligand
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Tnfrsf10b protein, mouse
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha
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Aspartate Aminotransferases
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Alanine Transaminase