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

Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results.
 ...
PMID:Use of an anti-interleukin-2 receptor monoclonal antibody for GVHD prophylaxis in unrelated donor BMT. 848 77

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.
 ...
PMID:The development of IL-2 conjugated liposomes for therapeutic purposes. 954 72

A 36-year-old woman was referred to our hospital because of leukocytosis in June 2000, and was admitted to our hospital and diagnosed as having adult T-cell leukemia/lymphoma (ATL; acute type). Complete remission was achieved with eight courses of CHOP therapy, but ATL relapsed and she was readmitted to our hospital in September 2001. Laboratory examination showed elevated levels of serum LDH and soluble IL-2 receptor, and hypercalcemia. CT examinations showed swelling of the abdominal lymph nodes and hepatosplenomegaly. CHOP therapy improved the symptoms, but recrudescence soon occurred. After two courses of salvage therapy which resulted in no remission, the patient received an allogeneic peripheral blood stem cell transplant (allo-PBSCT) from her HLA-matched sibling donor after preconditioning with BU + CY in January 31, 2002. Cyclosporin A (CsA) and short-term MTX were used to prevent GVHD. Bone marrow engraftment was prompt and acute GVHD was not found. Two months later, recurrence was seen in the form of subcutaneous tumors, but the tumors spontaneously disappeared following CsA withdrawal. At the time of writing, eight months after the transplant, remission has been maintained. A graft-versus-leukemia (GVL) effect may have been the curative action in this case.
 ...
PMID:[Cyclosporin A withdrawal causes spontaneous remission of recurrent subcutaneous tumors after allogeneic peripheral blood stem cell transplantation for adult T-cell leukemia/lymphoma]. 1269 82