Source:http://linkedlifedata.com/resource/pubmed/id/10519409
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
19
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| pubmed:dateCreated |
1999-11-4
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| pubmed:abstractText |
Vaccination with tumor-associated antigens is a promising approach for cancer immunotherapy. Because the majority of these antigens are normal self antigens, they may require suitable delivery systems to promote their immunogenicity. A recombinant vector based on the modified vaccinia virus Ankara (MVA) was used for expression of human tyrosinase, a melanoma-specific differentiation antigen, and evaluated for its efficacy as an antitumor vaccine. Stable recombinant viruses (MVA-hTyr) were constructed that have deleted the selection marker lacZ and efficiently expressed human tyrosinase in primary human cells and cell lines. Tyrosinase-specific human CTLs were activated in vitro by MVA-hTyr-infected, HLA-A*0201-positive human dendritic cells. Importantly, an efficient tyrosinase- and melanoma-specific CTL response was induced in vitro using MVA-hTyr-infected autologous dendritic cells as activators for peripheral blood mononuclear cells derived from HLA-A*0201-positive melanoma patients despite prior vaccination against smallpox. Immunization of HLA-A*0201/Kb transgenic mice with MVA-hTyr induced A*0201-restricted CTLs specific for the human tyrosinase-derived peptide epitope 369-377. These in vivo primed CTLs were of sufficiently high avidity to recognize and lyse human melanoma cells, which present the endogenously processed tyrosinase peptide in the context of A*0201. Tyrosinase-specific CTL responses were significantly augmented by repeated vaccination with MVA-hTyr. These findings demonstrate that HLA-restricted CTLs specific for human tumor-associated antigens can be efficiently generated by immunization with recombinant MVA vaccines. The results are an essential basis for MVA-based vaccination trials in cancer patients.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Genetic Markers,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Monophenol Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Smallpox Vaccine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
59
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4955-63
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10519409-Animals,
pubmed-meshheading:10519409-Cell Line,
pubmed-meshheading:10519409-Dendritic Cells,
pubmed-meshheading:10519409-Enzyme Induction,
pubmed-meshheading:10519409-Genetic Markers,
pubmed-meshheading:10519409-Genetic Vectors,
pubmed-meshheading:10519409-HLA-A Antigens,
pubmed-meshheading:10519409-Humans,
pubmed-meshheading:10519409-Lymphocyte Activation,
pubmed-meshheading:10519409-Melanoma,
pubmed-meshheading:10519409-Mice,
pubmed-meshheading:10519409-Mice, Transgenic,
pubmed-meshheading:10519409-Monophenol Monooxygenase,
pubmed-meshheading:10519409-Recombinant Fusion Proteins,
pubmed-meshheading:10519409-Sequence Deletion,
pubmed-meshheading:10519409-Smallpox Vaccine,
pubmed-meshheading:10519409-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:10519409-Transfection,
pubmed-meshheading:10519409-Vaccinia virus
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| pubmed:year |
1999
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| pubmed:articleTitle |
Modified vaccinia virus Ankara for delivery of human tyrosinase as melanoma-associated antigen: induction of tyrosinase- and melanoma-specific human leukocyte antigen A*0201-restricted cytotoxic T cells in vitro and in vivo.
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| pubmed:affiliation |
GSF-Institute for Molecular Virology, Munich, Germany. drexler@gsf.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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