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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-5-4
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pubmed:abstractText |
The inhibitor of apoptosis protein survivin is highly expressed in neuroblastoma (NB) and survivin-specific T cells were identified in Stage 4 patients. Therefore, we generated a novel survivin minigene DNA vaccine (pUS-high) encoding exclusively for survivin-derived peptides with superior MHC class I (H2-K(k)) binding affinities and tested its efficacy to suppress tumor growth and metastases in a syngeneic NB mouse model. Vaccination was performed by oral gavage of attenuated Salmonella typhimurium SL7207 carrying pUS-high. Mice receiving the pUS-high in the prophylactic setting presented a 48-52% reduction in s.c. tumor volume, weight and liver metastasis level in contrast to empty vector controls. This response was as effective as a survivin full-length vaccine and was associated with an increased target cell lysis, increased presence of CD8(+) T-cells at the primary tumor site and enhanced production of proinflammatory cytokines by systemic CD8(+) T cells. Furthermore, depletion of CD8(+) but not CD4(+) T-cells completely abrogated the pUS-high mediated primary tumor growth suppression, demonstrating a CD8(+) T-cell mediated effect. Therapeutic vaccination with pUS-high led to complete NB eradication in over 50% of immunized mice and surviving mice showed an over 80% reduction in primary tumor growth upon rechallenge in contrast to controls. In summary, survivin-based DNA vaccination is effective against NB and the rational minigene design provides a promising approach to circumvent potentially hazardous effects of using full length antiapoptotic genes as DNA vaccines.
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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/Birc5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1097-0215
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pubmed:author |
pubmed-author:BaykanBiancaB,
pubmed-author:BleekeMatthiasM,
pubmed-author:DurmusTahirT,
pubmed-author:FestStefanS,
pubmed-author:GaedickeGerhardG,
pubmed-author:HohnOliverO,
pubmed-author:HuebenerNicoleN,
pubmed-author:JaegerInes SIS,
pubmed-author:LodeHolger NHN,
pubmed-author:MichalskyElkeE,
pubmed-author:PreissnerRobertR,
pubmed-author:StermannAlexanderA,
pubmed-author:WeixlerSilkeS,
pubmed-author:WoehlerAnjaA,
pubmed-author:ZenclussenAna CAC
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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 |
104-14
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19291796-Animals,
pubmed-meshheading:19291796-Apoptosis,
pubmed-meshheading:19291796-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19291796-Cell Line, Tumor,
pubmed-meshheading:19291796-Cytokines,
pubmed-meshheading:19291796-Cytotoxicity, Immunologic,
pubmed-meshheading:19291796-Drug Design,
pubmed-meshheading:19291796-Female,
pubmed-meshheading:19291796-Flow Cytometry,
pubmed-meshheading:19291796-Histocompatibility Antigens Class I,
pubmed-meshheading:19291796-Immunoenzyme Techniques,
pubmed-meshheading:19291796-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:19291796-Mice,
pubmed-meshheading:19291796-Mice, Inbred A,
pubmed-meshheading:19291796-Microtubule-Associated Proteins,
pubmed-meshheading:19291796-Neuroblastoma,
pubmed-meshheading:19291796-Peptide Fragments,
pubmed-meshheading:19291796-RNA, Messenger,
pubmed-meshheading:19291796-Repressor Proteins,
pubmed-meshheading:19291796-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19291796-Vaccination,
pubmed-meshheading:19291796-Vaccines, DNA
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pubmed:year |
2009
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pubmed:articleTitle |
Survivin minigene DNA vaccination is effective against neuroblastoma.
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pubmed:affiliation |
Pediatrics, Experimental Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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