| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T19579 | ||||
| Target Name | Interleukin-2 receptor subunit beta | ||||
| Target Type | Clinical Trial |
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| Action against Disease Model | Medusa IL-2 | The potency of IL-2 is EC50 = 20.2+/-1.3 and 22.0+/-1.3 u/ml in Stimulation of natural killer activity in peripheral blood lymphocytes of healthy donors and melanoma patients respectively | [553281] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Lymphohematopoietic malignancies are common spontaneous diseases of dogs whose clinical presentation and biologic behavior closely resemble their h uMan counterparts. The goal of this study was to define the potential to use canine lymphoma and leukemia as suitable models to refine therapeutic approaches targeting the interleukin-2 receptor (IL-2R). The authors evaluated thepatterns of IL-2R expression in 13 dogs with multicentric non-Hodgkin's lymphoma (NHL) and in six dogs with leukemia (acute lymphocytic leukemia, n = 3; chronic lymphocytic leukemia in blast crisis, n = 1; acute monoblastic leukemia, n = 2). The authors first cloned and sequenced the complete coding domains of the wild-type canine IL-2R alpha-chain gene. They next used qualitative reverse transcription polymerase chain reaction (RT-PCR) analysis to examine IL-2R alpha, beta, and gamma(c) subunit expression in the t uMors. Messenger RNA (mRNA) for the interleukin-2 receptor alpha, beta, and gammac subunits that comprise the high-affinity receptor was present in samples from all dogs with NHL. Expression of functional surface IL-2R also was observed flow cytometrically in NHL cells from allfour dogs tested. Leukemic cells from one dog with B cell acute lymphocytic leukemia and two dogs with acute monoblastic leukemia expressed mRNA for all three subunits, whereas cells from another dogwith B cell leukemia and both dogs with T cell leukemia expressed only mRNA for the beta and gammac subunits that comprise the intermediate-affinity receptor. These results indicate that the IL-2R iscommonly expressed in canine lymphohematopoietic malignancies, and support the suitability of this large-animal model to evaluate targeted IL-2R cancer therapy using approaches of interest in the treatment of h uMans with hemolymphatic cancers. | [553281] | |||
| References | |||||
| Ref 553281 | Stimulation of natural killer activity in peripheral blood lymphocytes of healthy donors and melanoma patients in vitro: synergism between interleukin (IL)-12 and IL-15 or IL-12 and IL-2. Naunyn Schmiedebergs Arch Pharmacol. 1998 Sep;358(3):382-9. | ||||
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