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)

The autoreactive T cell plays a pivotal role in the pathogenesis of type I diabetes in humans and in rodent animal models. Elimination or attenuation of these cells may provide a means to treat the disease. The use of antibodies directed to T cells has shown varying degrees of effectiveness in the treatment of autoimmune disease. The use of a bifunctional antibody directed to T cells with a cytolytic agent may provide an additional level of therapeutic efficacy compared to anti-T-cell antibodies alone. To test this hypothesis, we prepared a bifunctional antibody (IVA039.1) with specificity for the mouse interleukin-2 (IL-2) receptor and vinca alkaloids. The antibody was derived from the fusion of vinca immune spleen cells with PC61 5.3, a hybridoma that produces rat anti-mouse IL-2 receptor antibody. IVA039.1 was purified by affinity chromatography through Protein A and anti-vinca affinity columns followed by TSK-DEAE high-pressure liquid chromatography (HPLC). Bifunctionality of the antibody was confirmed by fluorescence-activated cell sorting (FACS) analysis, enzyme-linked immunoadsorbent assay (ELISA) and a cell assay designed to measure simultaneously both IL-2 receptor and vinca reactivities. The biodistribution of IVA039.1 was determined in normal and streptozotocin-complete Freund's adjuvant (CFA) induced diabetic mice. Enhanced uptake of IVA039.1 was observed in the pancreata, spleens, and lymph nodes of diabetic compared to normal mice. These data suggest that bifunctional antibodies that can deliver cytolytic agents to T cells may be appropriate candidates for the treatment of diabetes and other autoimmune diseases.
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PMID:Production and in vivo characterization of a bifunctional antibody (IVA039.1) with specificity for the mouse interleukin-2 receptor and vinca alkaloids. 805 Jul 76

A unique immunoliposome has been developed as a drug delivery vehicle for immunotherapy. Human recombinant interleukin-2 (IL-2) has been chemically coupled to the external surface of small unilamellar vesicles (SUVs) containing methotrexate as a candidate immunosuppresive agent in order to specifically direct the drug-bearing liposome to activated T-cells expressing the high affinity IL-2 receptor. This drug delivery system is designed to deliver an immunosuppressive agent to those cells that actively participate in disorders such as graft rejection without delivering an effective but potentially toxic drug to all cells of the immune system as well as other healthy tissues. IL-2 was chemically modified with succinimidyl 4-[p-maleidophenyl butyrate](SMPB) while the receptor binding domain on IL-2 was protected by monoclonal anti-IL-2 bound to Protein A-Silica Gel. The antibody recognizes the receptor binding domain of the IL-2 molecule. The IL-2 was derivatized with S-succinimidyl-S-thioacetate (SATA) in order to add an acetyl thioester group to the lipid and create the complex. The derivatized lipid (SATA-PE) was then part of the liposome formulation containing DSPC:cholesterol: SATA-PE at a mole ratio of 1.5:1.0:0.26. SMPB-IL-2 was covalently coupled to the external surface of the SUV after deacetylation of the thioester moiety at pH 7.4 in PBS. Liposomes prepared by sonication or extrusion had an average diameter of 46-50 nm. SUV-IL-2 bound to the high affinity IL-2 receptor as measured by competitive binding assays and Scatchard analysis using 111InCl2-loaded liposomes The preparation exhibited a binding constant of 30 pM, consistent with values for free IL-2 cited in the literature. SUV IL-2 could be used as the sole source of IL-2 for the murine CTLL-2 T-cell line or for human mitogen-activated PBLs. The presence of IL-2 coupled to the surface was absolutely required for delivery of the drug to the cell. When methotrexate was encapsulated within the internal aqueous space, receptor-mediated endocytosis led to the inhibition of proliferation due to delivery of MTX to the cytoplasm of the cell. More than 90% of the methotrexate was retained within the liposome during storage over a 24-h period at 4 degrees C. This immunoliposome represents a new class of cell specific immunoliposomes whose entry into the cell is controlled by a cell surface receptor.
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PMID:The development of IL-2 conjugated liposomes for therapeutic purposes. 954 72