Source:http://linkedlifedata.com/resource/pubmed/id/20960189
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2011-1-28
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| pubmed:abstractText |
Survivin is overexpressed by 70-80% of pancreatic cancers, and is associated with resistance to chemotherapy and a poor prognosis. Gemcitabine has been a standard treatment for patients with advanced pancreatic cancer for a decade. Recent reports have demonstrated that gemcitabine treatment attenuates the tumor-suppressive environment by eliminating CD11b(+)/Gr-1(+) myeloid-derived suppressor cells (MDSCs). We hypothesize that a cancer vaccine targeting survivin can achieve enhanced efficacy when combined with gemcitabine. In this study, we tested this hypothesis using modified vaccinia Ankara (MVA) expressing full-length murine survivin. The poorly immunogenic mouse pancreas adenocarcinoma cell line, Pan02, which expresses murine survivin and is syngeneic to C57BL/6, was used for this study. Immunization with MVA-survivin resulted in a modest therapeutic antitumor effect on established Pan02 tumors. When administered with gemcitabine, MVA-survivin immunization resulted in significant tumor regression and prolonged survival. The enhanced vaccine efficacy was associated with decreased CD11b(+)/Gr-1(+) MDSCs. To analyze the survivin-specific immune response to MVA-survivin immunization, we utilized a peptide library of 15mers with 11 residues overlapping from full-length murine survivin. Splenocytes from mice immunized with MVA-survivin produced intracellular ?-interferon in response to in vitro stimulation with the overlapping peptide library. Increased survivin-specific CD8(+) T cells that specifically recognized the Pan02 tumor line were seen in mice treated with MVA-survivin and gemcitabine. These data suggest that vaccination with MVA-survivin in combination with gemcitabine represents an attractive strategy to overcome tumor-induced peripheral immune tolerance, and this effect has potential for clinical benefit in pancreatic cancer.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD11b,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Birc5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/gemcitabine,
http://linkedlifedata.com/resource/pubmed/chemical/granulocyte receptor 1, mouse
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1432-0851
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
60
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
99-109
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| pubmed:meshHeading |
pubmed-meshheading:20960189-Adenocarcinoma,
pubmed-meshheading:20960189-Animals,
pubmed-meshheading:20960189-Antigens, CD11b,
pubmed-meshheading:20960189-Antigens, Neoplasm,
pubmed-meshheading:20960189-CD8-Positive T-Lymphocytes,
pubmed-meshheading:20960189-Cancer Vaccines,
pubmed-meshheading:20960189-Cell Line, Tumor,
pubmed-meshheading:20960189-Deoxycytidine,
pubmed-meshheading:20960189-Genetic Vectors,
pubmed-meshheading:20960189-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:20960189-Interferon-gamma,
pubmed-meshheading:20960189-Lymphocyte Activation,
pubmed-meshheading:20960189-Mice,
pubmed-meshheading:20960189-Mice, Inbred C57BL,
pubmed-meshheading:20960189-Myeloid Cells,
pubmed-meshheading:20960189-Pancreatic Neoplasms,
pubmed-meshheading:20960189-Peptide Fragments,
pubmed-meshheading:20960189-Peptide Library,
pubmed-meshheading:20960189-Receptors, Cell Surface,
pubmed-meshheading:20960189-Remission Induction,
pubmed-meshheading:20960189-Repressor Proteins,
pubmed-meshheading:20960189-Vaccination,
pubmed-meshheading:20960189-Vaccinia virus
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| pubmed:year |
2011
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| pubmed:articleTitle |
Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model.
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| pubmed:affiliation |
Division of General and Oncologic Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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