Linked Life Data

10096292

Source:http://linkedlifedata.com/resource/pubmed/id/10096292

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-7-12
pubmed:abstractText
We converted a model, syngeneic, nonimmunogenic tumor antigen into a vaccine by fusing it with a proinflammatory chemokine. Two chemokines, interferon inducible protein 10 and monocyte chemotactic protein 3, were fused to lymphoma Ig variable regions (sFv). The sFv-chemokine fusion proteins elicited chemotactic responses in vitro and induced inflammatory responses in vivo. Furthermore, in two independent models, vaccination with DNA constructs encoding the corresponding fusions generated superior protection against a large tumor challenge (20 times the minimum lethal dose), as compared with the best available protein vaccines. Immunity was not elicited by controls, including fusions with irrelevant sFv; fusions with a truncated chemokine that lacked receptor binding and chemotactic activity; mixtures of free chemokine and sFv proteins; or naked DNA plasmid vaccines encoding unlinked sFv and chemokine. The requirement for linkage of conformationally intact sFv and functionally active chemokine strongly suggested that the mechanism underlying these effects was the novel targeting of antigen presenting cells (APC) for chemokine receptor-mediated uptake of antigen, rather than the simple recruitment of APC to tumor by the chemokine. Finally, in addition to superior potency, these fusions were distinguished from lymphoma Ig fusions with granulocyte-macrophage colony-stimulating factor or other cytokines by their induction of critical effector T cells.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1087-0156
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
253-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10096292-Animals, pubmed-meshheading:10096292-Antigen-Presenting Cells, pubmed-meshheading:10096292-Binding, Competitive, pubmed-meshheading:10096292-Cancer Vaccines, pubmed-meshheading:10096292-Chemokine CCL7, pubmed-meshheading:10096292-Chemokine CXCL10, pubmed-meshheading:10096292-Chemokines, pubmed-meshheading:10096292-Chemokines, CXC, pubmed-meshheading:10096292-Chemotaxis, pubmed-meshheading:10096292-Cytokines, pubmed-meshheading:10096292-Dose-Response Relationship, Immunologic, pubmed-meshheading:10096292-Female, pubmed-meshheading:10096292-Flow Cytometry, pubmed-meshheading:10096292-Gene Therapy, pubmed-meshheading:10096292-Immunoglobulin Variable Region, pubmed-meshheading:10096292-Inflammation, pubmed-meshheading:10096292-Lymphoma, pubmed-meshheading:10096292-Mice, pubmed-meshheading:10096292-Mice, Inbred BALB C, pubmed-meshheading:10096292-Mice, Inbred C3H, pubmed-meshheading:10096292-Microscopy, Confocal, pubmed-meshheading:10096292-Monocyte Chemoattractant Proteins, pubmed-meshheading:10096292-Rats, pubmed-meshheading:10096292-Recombinant Fusion Proteins, pubmed-meshheading:10096292-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10096292-T-Lymphocytes
pubmed:year
1999
pubmed:articleTitle
Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity.
pubmed:affiliation
Science Application International Corporation, National Cancer Institute, Frederick, MD 21702, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.