Source:http://linkedlifedata.com/resource/pubmed/id/10491008
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
1999-10-21
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| pubmed:abstractText |
High affinity IL-2R5 is present on recently activated but not on resting or memory T cells. Selective targeting of T cells bearing high affinity IL-2R is an attractive therapy for many T cell-dependent cytopathic disease processes. A variety of rodent mAbs directed against the alpha-chain of the IL-2R, as well as IL-2 fusion toxins, have been used in animals and humans to achieve selective immunosuppression. Here we report on the development of a novel IL-2R targeting agent, a cytolytic chimeric IL-2/Fc fusion protein. This immunoligand binds specifically and with high affinity to IL-2R and is structurally capable of recruiting host Ab-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity activities. The Ig component ensures an extended circulating t1/2 of 25 h following systemic administration. To subsequently explore the mechanisms of the antidiabetogenic effects of IL-2/Fc, we have mutated the FcR binding and complement C1q binding (Fc-/-) domains of the Fc fragment to render the Fc unable to direct Ab-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity activities. In a model of passive transfer of diabetes in nonobese diabetic mice, lytic IL-2/Fc, but not nonlytic IL-2/Fc-/-, exhibited striking antidiabetogenic effects. Together with the negligible potential of IL-2/Fc for immunogenicity, this finding forecasts that cytolytic IL-2/Fc may offer a new therapeutic approach for selective targeting of auto and alloimmune T cells.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fc Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
163
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4041-8
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10491008-Adoptive Transfer,
pubmed-meshheading:10491008-Animals,
pubmed-meshheading:10491008-Antibodies, Monoclonal,
pubmed-meshheading:10491008-Antigens, CD4,
pubmed-meshheading:10491008-Blotting, Western,
pubmed-meshheading:10491008-CD4 Lymphocyte Count,
pubmed-meshheading:10491008-Cytotoxicity, Immunologic,
pubmed-meshheading:10491008-Diabetes Mellitus, Type 1,
pubmed-meshheading:10491008-Female,
pubmed-meshheading:10491008-Gene Targeting,
pubmed-meshheading:10491008-Gene Therapy,
pubmed-meshheading:10491008-Half-Life,
pubmed-meshheading:10491008-Immunoglobulin Fc Fragments,
pubmed-meshheading:10491008-Injections, Intraperitoneal,
pubmed-meshheading:10491008-Interleukin-2,
pubmed-meshheading:10491008-Lymphocyte Depletion,
pubmed-meshheading:10491008-Male,
pubmed-meshheading:10491008-Mice,
pubmed-meshheading:10491008-Mice, Inbred BALB C,
pubmed-meshheading:10491008-Mice, Inbred NOD,
pubmed-meshheading:10491008-Receptors, Interleukin-2,
pubmed-meshheading:10491008-Recombinant Fusion Proteins
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| pubmed:year |
1999
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| pubmed:articleTitle |
IL-2 receptor-targeted cytolytic IL-2/Fc fusion protein treatment blocks diabetogenic autoimmunity in nonobese diabetic mice.
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| pubmed:affiliation |
Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|