Linked Life Data

10096292

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

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pubmed-article:10096292pubmed:abstractTextWe 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.lld:pubmed
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pubmed-article:10096292pubmed:articleTitleGenetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity.lld:pubmed
pubmed-article:10096292pubmed:affiliationScience Application International Corporation, National Cancer Institute, Frederick, MD 21702, USA.lld:pubmed
pubmed-article:10096292pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10096292pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:10096292pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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