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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2009-10-5
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pubmed:abstractText |
Transforming growth factor-beta (TGF-beta) is a cytokine with potent immunosuppressive effects and is overexpressed in many tumors. Therefore, development of molecules able to inhibit TGF-beta is of paramount importance to improve the efficacy of antitumor immunotherapy. TGF-beta inhibitor peptides P144 and P17 were combined with the administration of adjuvant molecules poly(I:C) and agonistic anti-CD40 antibodies, and their effect on the growth of E.G7-OVA established tumors and on antitumor immune response was evaluated. Tumor rejection efficacy of a single administration of adjuvants was enhanced from 15 to 70 % when combined with repeated injections of TGF-beta inhibitor peptides. Simultaneous administration of adjuvants and TGF-beta inhibitor peptides was required for maximal therapeutic efficacy. Although tumor cells produced TGF-beta, it was found that the beneficial effect of peptide administration was mainly due to the inhibition of TGF-beta produced by regulatory CD4(+)CD25(+) T cells rather than by tumor cells. The enhanced antitumor effect was accompanied by a higher activity of dendritic cells, natural killer cells and tumor antigen-specific T cells, as well as by a decrease in the number of myeloid-derived suppressor cells. In conclusion, administration of peptide inhibitors of TGF-beta in therapeutic vaccination enhances the efficacy of immunotherapy by increasing antitumor immune responses. These peptide inhibitors may have important applications for current immunotherapeutic strategies.
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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/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Poly I-C,
http://linkedlifedata.com/resource/pubmed/chemical/RAG-1 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta1 type III receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-0215
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pubmed:author |
pubmed-author:ArandaFernandoF,
pubmed-author:BerraondoPedroP,
pubmed-author:BezunarteaJaioneJ,
pubmed-author:Borrás-CuestaFranciscoF,
pubmed-author:Díaz-ValdésNancyN,
pubmed-author:DotorJavierJ,
pubmed-author:LasarteJuan JoséJJ,
pubmed-author:LlopizDianaD,
pubmed-author:PflichthoferDD,
pubmed-author:PrietoJesúsJ,
pubmed-author:RuizMartaM,
pubmed-author:SarobePabloP
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
125
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2614-23
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pubmed:meshHeading |
pubmed-meshheading:19530254-Adjuvants, Immunologic,
pubmed-meshheading:19530254-Animals,
pubmed-meshheading:19530254-Antigens, CD40,
pubmed-meshheading:19530254-Dendritic Cells,
pubmed-meshheading:19530254-Female,
pubmed-meshheading:19530254-Flow Cytometry,
pubmed-meshheading:19530254-Homeodomain Proteins,
pubmed-meshheading:19530254-Humans,
pubmed-meshheading:19530254-Immunotherapy,
pubmed-meshheading:19530254-Killer Cells, Natural,
pubmed-meshheading:19530254-Melanoma, Experimental,
pubmed-meshheading:19530254-Mice,
pubmed-meshheading:19530254-Mice, Inbred C57BL,
pubmed-meshheading:19530254-Mice, Knockout,
pubmed-meshheading:19530254-Ovalbumin,
pubmed-meshheading:19530254-Peptide Fragments,
pubmed-meshheading:19530254-Poly I-C,
pubmed-meshheading:19530254-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:19530254-Survival Rate,
pubmed-meshheading:19530254-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:19530254-T-Lymphocytes, Regulatory,
pubmed-meshheading:19530254-Transforming Growth Factor beta,
pubmed-meshheading:19530254-Tumor Cells, Cultured
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pubmed:year |
2009
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pubmed:articleTitle |
Peptide inhibitors of transforming growth factor-beta enhance the efficacy of antitumor immunotherapy.
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pubmed:affiliation |
Division of Hepatology and Gene Therapy, University of Navarra, Center for Applied Medical Research (CIMA), Pamplona, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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