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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2006-6-8
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pubmed:abstractText |
Tumor-cell apoptosis is the basis of many cancer therapies, and tumor-specific T cells are the principal effectors of successful antitumor immunotherapies. Here we show that induction of tumor-cell apoptosis by an agonistic monoclonal antibody to DR5, the apoptosis-inducing receptor for TNF-related apoptosis-inducing ligand (TRAIL), combined with T-cell activation by agonistic monoclonal antibodies to the costimulatory molecules CD40 and CD137, potently and rapidly stimulated tumor-specific effector CD8+ T cells capable of eradicating preestablished tumors. Primary fibrosarcomas initiated with the carcinogen 3-methylcholanthrene (MCA), multiorgan metastases and a primary tumor containing as many as 90% tumor cells resistant to DR5-specific monoclonal antibody were rejected without apparent toxicity or induction of autoimmunity. This combination therapy of three monoclonal antibodies (trimAb) rapidly induced tumor-specific CD8+ T cells producing interferon (IFN)-gamma in the tumor-draining lymph node, consistent with a crucial requirement for CD8+ T cells and IFN-gamma in the tumor rejection process. These results in mice indicate that a rational monoclonal antibody-based therapy that both causes tumor-cell apoptosis through DR5 and activates T cells may be an effective strategy for cancer immunotherapy in humans.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, TNF-Related...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf10b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf10 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
693-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16680149-Animals,
pubmed-meshheading:16680149-Antibodies, Monoclonal,
pubmed-meshheading:16680149-Apoptosis,
pubmed-meshheading:16680149-Apoptosis Regulatory Proteins,
pubmed-meshheading:16680149-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16680149-Cell Line, Tumor,
pubmed-meshheading:16680149-Interferon-gamma,
pubmed-meshheading:16680149-Lymphocyte Activation,
pubmed-meshheading:16680149-Membrane Glycoproteins,
pubmed-meshheading:16680149-Mice,
pubmed-meshheading:16680149-Mice, Inbred BALB C,
pubmed-meshheading:16680149-Mice, Knockout,
pubmed-meshheading:16680149-Mice, SCID,
pubmed-meshheading:16680149-Neoplasm Transplantation,
pubmed-meshheading:16680149-Neoplasms,
pubmed-meshheading:16680149-Receptors, TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:16680149-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:16680149-Survival Rate,
pubmed-meshheading:16680149-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:16680149-Tumor Necrosis Factor-alpha
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pubmed:year |
2006
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pubmed:articleTitle |
Eradication of established tumors in mice by a combination antibody-based therapy.
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pubmed:affiliation |
Department of Immunology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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