Source:http://linkedlifedata.com/resource/pubmed/id/17726460
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2007-10-19
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pubmed:abstractText |
Immunity to self antigens on cancer is constrained by tolerance/ignorance. DNA vaccines encoding xenogeneic differentiation antigens, such as tyrosinase (TYR), mediate tumor protection and regression in implantable mouse models, and dogs with spontaneous melanoma. We conducted a trial of mouse and human TYR DNA vaccines in stage III/IV melanoma patients. Eighteen human leukocyte antigen (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received three mouse TYR DNA injections followed by three human TYR DNA injections; the other group received the same vaccines in opposite sequence. The study was conducted at three dose levels: 100, 500, and 1,500 microg DNA/injection, administered intramuscularly (IM) every 3 weeks. Most toxicities were grade 1 injection site reactions. Seven patients developed CD8(+) T-cell responses, defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or intracellular cytokine staining (ICS) assays. There was found to be no relationship between dose, assigned schedule, and T-cell response. At a median of 42 months follow-up, median survival has not been reached. Mouse and human TYR DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 patients. T cells recognizing a native TYR peptide had a phenotype consistent with that of effector memory cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1525-0016
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pubmed:author |
pubmed-author:ChapmanPaul BPB,
pubmed-author:GallardoHumilidad FHF,
pubmed-author:HeywoodMelanieM,
pubmed-author:HoughtonAlan NAN,
pubmed-author:KrownSusan ESE,
pubmed-author:LivingstonPhilip OPO,
pubmed-author:PanageasKatherine SKS,
pubmed-author:PeralesMiguel AMA,
pubmed-author:RanganathanRajaramR,
pubmed-author:RasalanTeresa STS,
pubmed-author:RiviereIsabelleI,
pubmed-author:TerzulliStephanie LSL,
pubmed-author:WangJianJ,
pubmed-author:WolchokJedd DJD,
pubmed-author:YuanJiandaJ,
pubmed-author:ZhangYanY
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pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2044-50
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pubmed:meshHeading |
pubmed-meshheading:17726460-Adult,
pubmed-meshheading:17726460-Aged,
pubmed-meshheading:17726460-Animals,
pubmed-meshheading:17726460-Antibodies,
pubmed-meshheading:17726460-CD8-Positive T-Lymphocytes,
pubmed-meshheading:17726460-Drug Toxicity,
pubmed-meshheading:17726460-Humans,
pubmed-meshheading:17726460-Immunogenetics,
pubmed-meshheading:17726460-Immunotherapy,
pubmed-meshheading:17726460-Melanoma,
pubmed-meshheading:17726460-Mice,
pubmed-meshheading:17726460-Middle Aged,
pubmed-meshheading:17726460-Monophenol Monooxygenase,
pubmed-meshheading:17726460-Neoplasm Staging,
pubmed-meshheading:17726460-Phenotype,
pubmed-meshheading:17726460-Survival Rate,
pubmed-meshheading:17726460-Vaccines, DNA
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pubmed:year |
2007
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pubmed:articleTitle |
Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma.
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pubmed:affiliation |
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. wolchokj@mskcc.org
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pubmed:publicationType |
Journal Article,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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