Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1991-5-6
|
| pubmed:abstractText |
High-affinity interleukin 2 receptors (IL-2Rs) are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac-M, a murine monoclonal antibody specific for the IL-2R alpha chain, was used to inhibit organ allograft rejection. However, the use of murine anti-Tac as an immunosuppressive agent was limited by neutralization by human anti-murine antibodies and by weak recruitment of effector functions. To circumvent these difficulties, a humanized antibody to the IL-2R, anti-Tac-H, was prepared. This molecule is human with the exception of the hypervariable segments, which are retained from the mouse. In vivo survival of anti-Tac-H is 2.5-fold longer than simultaneously administered anti-Tac-M (terminal t1/2, 103 hr vs. 38 hr). In addition, anti-Tac-H is less immunogenic than anti-Tac-M when administered to cynomolgus monkeys undergoing heterotopic cardiac allografting. Specifically, all monkeys treated with anti-Tac-M developed measurable anti-anti-Tac-M levels by day 15 (mean onset, 11 days). In contrast, none of the animals receiving anti-Tac-H produced measurable antibodies to this monoclonal antibody before day 33. Finally, there was a prolongation of graft survival in the cynomolgus heterotopic cardiac allograft model in animals receiving anti-Tac. In animals that received anti-Tac-M, the allograft survival was prolonged compared to that of the control group (mean survival, 14 +/- 1.98 days compared to 9.2 +/- 0.48 days; P less than 0.025). Graft survival was further prolonged by anti-Tac-H with a mean survival of 20.0 +/- 0.55 days (compared to controls, P less than 0.001; compared to anti-Tac-M, P less than 0.02). There was no toxicity attributable to the administration of either form of anti-Tac. Thus, anti-Tac-H significantly prolonged allograft survival in primates, without toxic side effects, and may be of value as an adjunct to standard immunosuppressive therapy in humans.
|
| pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-13293164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2238051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2406013,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2408992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2513570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2673025,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2726771,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2846094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2884454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-2904526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-3008337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-3121594,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-3124608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-3126026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-3908687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-3925068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-4186070,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-5443170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-6408186,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-6970774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2011577-814165
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0027-8424
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
88
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
2663-7
|
| pubmed:dateRevised |
2009-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:2011577-Animals,
pubmed-meshheading:2011577-Antibodies, Monoclonal,
pubmed-meshheading:2011577-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:2011577-Graft Survival,
pubmed-meshheading:2011577-Heart Transplantation,
pubmed-meshheading:2011577-Macaca fascicularis,
pubmed-meshheading:2011577-Receptors, Interleukin-2,
pubmed-meshheading:2011577-Transplantation, Homologous
|
| pubmed:year |
1991
|
| pubmed:articleTitle |
Anti-Tac-H, a humanized antibody to the interleukin 2 receptor, prolongs primate cardiac allograft survival.
|
| pubmed:affiliation |
Surgery Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
|
| pubmed:publicationType |
Journal Article
|