Linked Life Data

16707471

Source:http://linkedlifedata.com/resource/pubmed/id/16707471

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-5-18
pubmed:abstractText
Malignant melanoma is an attractive model disease for the development of antigen-specific immunotherapy because many antigens recognized by tumor-specific T cells have been identified. In C57BL/6 mice, genetic immunization with recombinant adenovirus encoding xenogeneic human tyrosinase-related protein 2 (Ad-hTRP2) induces protective but not therapeutic cellular immunity against growth of transplanted B16 melanoma cells. Here, we additionally applied CpG DNA and synthetic double-stranded RNA, which activate the innate immune system via Toll-like receptors (TLR). Both adenoviral vaccination and peritumoral injections of TLR ligands were required for rejection of established B16 melanoma in the skin. To more closely mimic the clinical situation in patients with melanoma, we evaluated this combined immunotherapeutic strategy in genetically modified mice, which overexpress hepatocyte growth factor (HGF) and carry an oncogenic mutation in the cyclin-dependent kinase 4 (CDK4)(R24C). HGF x CDK4(R24C) mice rapidly develop multiple invasive melanomas in the skin following neonatal carcinogen treatment, which spontaneously metastasize to lymph nodes and lungs. Vaccination with Ad-hTRP2 followed by injections of TLR ligands resulted in delayed growth of autochthonous primary melanomas in the skin and reduction in the number of spontaneous lung metastases but did not induce tumor regression. Carcinogen-treated HGF x CDK4(R24C) mice bearing multiple autochthonous melanomas did not reject transplanted B16 melanoma despite treatment with Ad-hTRP2 and TLR ligands, suggesting the development of tumor immunotolerance. Further investigations in our novel genetic melanoma model may help to better understand the role of the immune system in the pathogenesis and treatment of this life-threatening disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5427-35
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16707471-Adenoviridae, pubmed-meshheading:16707471-Animals, pubmed-meshheading:16707471-Cancer Vaccines, pubmed-meshheading:16707471-CpG Islands, pubmed-meshheading:16707471-Cyclin-Dependent Kinase 4, pubmed-meshheading:16707471-Epitopes, pubmed-meshheading:16707471-Female, pubmed-meshheading:16707471-Hepatocyte Growth Factor, pubmed-meshheading:16707471-Humans, pubmed-meshheading:16707471-Intramolecular Oxidoreductases, pubmed-meshheading:16707471-Lung Neoplasms, pubmed-meshheading:16707471-Male, pubmed-meshheading:16707471-Melanoma, Experimental, pubmed-meshheading:16707471-Mice, pubmed-meshheading:16707471-Mice, Inbred C57BL, pubmed-meshheading:16707471-Mice, Transgenic, pubmed-meshheading:16707471-Poly I-C, pubmed-meshheading:16707471-Skin Neoplasms, pubmed-meshheading:16707471-Toll-Like Receptors, pubmed-meshheading:16707471-Vaccines, DNA
pubmed:year
2006
pubmed:articleTitle
Therapeutic efficacy of antigen-specific vaccination and toll-like receptor stimulation against established transplanted and autochthonous melanoma in mice.
pubmed:affiliation
Laboratory of Experimental Dermatology, Department of Dermatology, University of Bonn, Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't