Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental and clinical studies have been carried out to investigate the application of a number of monoclonal antibodies which recognise human lymphocytes in clinical organ transplantation. Where possible, preliminary studies have been carried out using a primate renal allograft model before proceeding to clinical pilot studies. The Campath-1 antigen (CDW52) appears to be a good target for antilymphocytic therapy; a powerful immunosuppressive effect has been demonstrated using both IgM and IgG2b antibodies which recognise this antigen. An IgG2b antibody which recognises the IL-2 receptor was shown to be immunosuppressive in the primate model but clinical studies have, as yet not demonstrated a significant, beneficial effect in preventing rejection. Patients who receive antilymphocyte monoclonal antibodies require monitoring of the expression of the target antigen, the level of free antibody in serum and the development of an antiglobulin response. The current issues in the use of antilymphocyte monoclonal antibodies in clinical immunosuppression include identification of the optimum target, interaction of the antibody with recipient effector mechanisms and methods to avoid or suppress the antiglobulin response.
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PMID:Monoclonal antibodies in immunosuppression. 179 64

Rheumatoid arthritis is a chronic inflammatory disease. Established treatment is limited because of the clinical response or the induction of adverse effects. New biological agents evaluated for treatment of rheumatoid arthritis have shown varied clinical success. These agents target cytokines such as tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1 or IL-6, or cell surface molecules such as CD4, CD5, CD7, IL-2 receptor, CDw52 or CD54. Amongst these new drugs, only a few have shown clinical effectiveness in double-blind placebo-controlled trials. These include the primatised nondepleting anti-CD4 monoclonal antibody (mAb) CE9.1 (keliximab), the TNFalpha-blocking mAbs cA2 (infliximab) and CDP-571, the human recombinant soluble TNFalpha receptors p55 (lenercept) and p80, as well as the human recombinant IL-1 receptor antagonist protein, anakinra. Thus, only these agents qualify for evaluation of combination treatment in rheumatoid arthritis. Rationales for combination therapy include: combining drugs with different sites of action to increase efficacy or with different toxicities to minimise risk; combining drugs with different kinetics, thus improving clinical activity; using a combination of drugs for the prevention of tachyphylaxis; or using a second drug which helps to prevent or delay the development of resistance to the first one. In addition, combination therapy could help to prevent or minimise adverse effects caused by treatment with biological agents. Based on knowledge from trials with biological agents, and on the different properties attributed to the established disease-modifying antirheumatic drugs (DMARDs) in ex vivo and in vitro studies, we propose evaluation of the following combination regimens involving biological agents. First, biological agents targeting TNFalpha (such as the mAbs cA2 or CDP-571, or the TNFalpha receptor p55-IgG1 fusion protein) given as a single infusion for rapid clinical response could be followed by continuation treatment with methotrexate, possibly combined with chloroquine, azathioprine or cyclosporin. Combination of specific anti-TNFalpha strategies with sulfasalazine should be avoided because of the induction of double-stranded DNA antibodies seen after TNFalpha blockade in vivo and reports on a systemic lupus erythematosus-like syndrome as an adverse effect during treatment with biological agents directed against TNFalpha or with sulfasalazine. Alternatively, continuous inhibition of TNFalpha or IL-1 with TNFalpha receptor p80-IgG1 fusion protein or IL-1 receptor antagonist, respectively, could be combined with methotrexate, with the disadvantage of a slower initial improvement of clinical symptoms. Combination regimens with the primatised CD4 mAb could include methotrexate as concomitant medication, with chloroquine or sulfasalazine as additional medication. Importantly, combination of different biological agents might induce more severe adverse effects than seen with monotherapy. Thus, protocols involving combinations of biological agents with established DMARDs promise better acceptance than combinations of 2 new and as yet unestablished drugs with possibly synergistic adverse effects because of their antigenic properties.
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PMID:Biological agents in rheumatoid arthritis: which ones could be used in combination? 1802 May 67