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 Nb2 rat lymphoma cell line has the unique property that its growth is dependent on lactogenic pituitary hormones. Cell surface staining with monoclonal antibodies showed expression of class I MHC alloantigens of the RT1u haplotype, but no expression of class II MHC antigens. Staining for differentiation markers was strongly positive with antibodies OX52, W3/13 and OX44. Partial and weaker staining was obtained with CD2, P4/16 and the transferrin receptor. Nb2 cells were negative with CD5, OX40 and CD4, whilst CD8 stained only a minor fraction (1%) and certain variant clones of the cell line. This general pattern of staining is consistent with the phenotype of a small subpopulation of immature T cells. Nb2 cells proliferated in response to recombinant human IL-2, although they did not stain with antibodies against the IL-2 receptor. Enhancement of the stimulation by IL-2 in the presence of a submitogenic concentration of hGH indicated a synergism between these two hormones, and responses were suppressed by a similar dose of cyclosporin A (ID50=2 microg/ml). Although IL-2 could not be identified in culture supernatants, the presence of mRNA for IL-2, IL-2R and IL-4 was demonstrated by dot blot analysis. Finally, evidence that the Nb2 lymphoma is of T-cell lineage was given by Northern blot detection of mRNA for the alpha and beta chains of the T-cell receptor.
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PMID:The phenotypic and molecular characterization of Nb2 lymphoma cells activated with IL-2 and human growth hormone. 1549 67

Denileukin diftitox, a genetically engineered fusion protein combining the enzymatically active domains of diphtheria toxin and the full-length sequence for interleukin-2 (IL-2), efficiently targets lymphoma cells expressing the high-affinity IL-2 receptor (IL-2R) consisting of the alpha/p55/CD25, beta/p75/CD122, and gamma/p64/CD132 chains. In vitro studies demonstrated that the retinoid X receptor (RXR) retinoid, bexarotene, at biologically relevant concentrations of 10(-6) M to 10(-8) M, upregulated both the p55 and p75 subunits of the IL-2R and enhanced 5- to 10-fold the susceptibility of T-cell leukemia cells to denileukin diftitox. To determine whether this biomodulatory effect could be recapitulated in vivo, we treated 14 patients with relapsed or refractory cutaneous T-cell lymphoma with escalating doses of bexarotene (75 mg/day-300 mg/day) and denileukin diftitox (18 mcg/kg per day x 3 days every 21 days) in a phase 1 trial. Overall response was 67% (4 complete responses, 4 partial responses). Modulation of IL-2R expression was observed at or above a bexarotene dose of 150 mg/day. Four patients experienced grade 2 or 3 leukopenia, and 2 had grade 4 lymphopenia. Our results demonstrate that the combination of denileukin diftitox and bexarotene is well tolerated and that even low doses (150 mg/day) of bexarotene are capable of in vivo upregulation of CD25 expression on circulating leukemia cells.
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PMID:A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. 1581 59

Previously we have demonstrated that a recombinant Newcastle disease virus (NDV) carrying the transgene EGFP can be retargeted to IL-2 receptor positive tumor cells by a bispecific fusion protein alphaHN-IL-2 in vitro. The purpose of the present study was to investigate the specificity and efficiency of gene delivery to tumor cells in vivo via this modified RNA virus. Prior ex vivo infection of murine lymphoma cells by the modified virus resulted in selective EGFP expression in IL-2R+ target tumor cells in vivo. Direct fluorescence microscopy and immunohistology showed viral replication in target positive tumor tissue resulting in much more EGFP expression than in target negative tumor tissue, 24 h after intratumoral injection of the alphaHN-IL-2 modified NDV. A quantitative real-time RT-PCR for EGFP mRNA. confirmed the selective gene expression in IL-2R+ tumor cells. Biodistribution studies showed that EGFP transgene delivery was reduced by 35-100% in liver, spleen, kidney, lung and thymus by the modified virus, while 98% of the transgene was delivered to IL-2R+ tumors. In conclusion, the modification of NDV by the bispecific protein does not compromise severely the efficiency of gene delivery into IL-2R-positive tumors, but greatly reduces viral gene expression in IL-2R-negative tumors and in normal tissues.
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PMID:Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein. 1601 Apr 18

We report the rare adult case of upper cervical spinal tumor diagnosed precursor B cell lymphoblastic lymphoma. A 48- year-old male had suffered from right neck pain and swelling for two months. He had no neurological symptoms. The serum level of IL-2 receptor was high (1,820 U/ml). The radiological examinations including MRI showed the tumor extending from right neck to the epidural space from medulla to the C4 level. The pathological diagnosis of biopsy specimens was malignant lymphoma. Since the early pre-B lymphoblast antigens were positive by the flow cytometry, the diagnosis was precursor B cell lymphoblastic lymphoma. This type of lymphoma is highly aggressive. The intensive chemotherapy regimen such as hyper-CVAD was superior to the lymphoma-like regimens. In the case showed the progressive neurological symptoms such as myelopathy and urinary incontinence, the immediate surgical decompression of the spinal cord may be necessary. Measurement of IL-2 receptor and biopsy with flow cytometry were necessary to work out the treatment strategy of the spinal malignant lymphoma. In this case, the complete response (CR) of the tumor was achieved with hyper-CVAD regimen and radiation therapy.
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PMID:[An adult case of precursor B cell lymphoblastic lymphoma extending from right neck to upper cervical spinal region]. 1627 25

Denileukin diftitox (Ontak) is a fusion protein comprising a diphtheria toxin and an interleukin (IL)-2 moiety that specifically targets CD25 (IL-2 receptor)-positive tumour cells. We report a patient with rapidly progressive Epstein-Barr virus-positive nasal type extranodal natural killer/T-cell lymphoma (extranodal NKTCL), treated with a combination of denileukin diftitox (Ontak) and oral bexarotene (Targretin). A significant regression of the cutaneous tumours was observed already after the first cycle of denileukin diftitox and was maintained for a period of 5 months with monthly cycles of denileukin diftitox. The treatment was well tolerated. Following this response the patient decided to stop the treatment. He was then followed by his oncologist and lost from dermatological follow-up. Shortly after treatment withdrawal the disease progressed and the patient received one cycle of doxorubicin (Caelyx). He died from septic shock syndrome 2 months later. To our knowledge this is the first case of extranodal NKTCL treated with denileukin diftitox and bexarotene. A striking, albeit transient, response occurred with this therapy. Combination treatment with denileukin diftitox and bexarotene should be further assessed in this aggressive type of cutaneous lymphoma.
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PMID:Regression of extranodal natural killer/T-cell lymphoma, nasal type with denileukin diftitox (Ontak) and bexarotene (Targretin): report of a case. 1663 8

Inhibition of the interleukin-2 (IL-2) pathway has potent immunosuppressive activity in humans as is evident from the broad therapeutic utility of cyclosporine, rapamycin, tacrolimus, and monoclonal antibodies blocking the high-affinity subunit of the IL-2 receptor (CD25). Here we describe a humanized antibody, MT204, interfering with IL-2 signaling by a novel mechanism. Although MT204 did not prevent IL-2 from binding to CD25, it potently antagonized downstream signaling events of IL-2 at sub-nanomolar concentrations, such as STAT3 tyrosine phosphorylation, expression of CD124, production of gamma-interferon and cell proliferation. While MT204 and the anti-CD25 mAb daclizumab were equally effective in inhibiting autocrine growth of human CD4(+) T cells, MT204 was far superior in preventing proliferation of NKL lymphoma cells, production of gamma-interferon by natural killer (NK) cells and proliferation of primary NK cells. MT204 has potential as a novel immunosuppressive and anti-proliferative therapy with an apparently broader spectrum of activities than anti-CD25 antibodies.
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PMID:A humanized monoclonal antibody against interleukin-2 that can inactivate the cytokine/receptor complex. 1700 2

A 66-year-old man came to us with a chief complaint of painful right scrotal swelling. The right testis was enlarged on the ultrasound gray scale, but the inside was homogeneous. A power Doppler ultrasound showed slightly increased vascular flow in the periphery of the right testis. As the soluble IL-2 receptor was 527 U/ml (normal: 220-530 U/ml), we considered malignant lymphoma and performed high orchiectomy. On pathological examination, the tumor was diagnosed as granulomatous orchitis. To our knowledge, this is the 21st case in Japan.
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PMID:[A case of granulomatous orchitis]. 1713 75

Twenty-five years ago, we reported the production of the monoclonal antibody, anti-Tac that identifies the IL-2 receptor alpha subunit and blocks the interaction of IL-2 with this growth factor receptor. In 1997, daclizumab (Zenapax), the humanized form of this antibody, was approved by the FDA for use in the prevention of renal allograft rejection. In addition, we demonstrated that daclizumab is of value in the treatment of patients with noninfectious uveitis, multiple sclerosis, and the neurological disease human T-cell lymphotropic virus I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Others demonstrated therapeutic efficacy with daclizumab in patients with pure red cell aplasia, aplastic anemia, and psoriasis. Thus, translation of basic insights concerning the IL-2/IL-2 receptor system obtained using the monoclonal antibody daclizumab provided a useful strategy for the prevention of organ allograft rejection and the treatment of patients with select autoimmune diseases or T-cell leukemia/lymphoma.
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PMID:Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. 1721 65

Daclizumab (Zenapax) identifies the alpha subunit of the interleukin-2 (IL-2) receptor and blocks the interaction of this cytokine with its growth factor receptor. The scientific basis for the choice of the IL-2 receptor alpha subunit as a target for monoclonal antibody-mediated therapy of leukemia/lymphoma is that very few normal cells express IL-2R alpha, whereas the abnormal T cells in patients with an array of lymphoid malignancies express this receptor. In 1997, daclizumab was approved by the FDA for use in the prevention of renal allograft rejection. In addition, anti-Tac provided effective therapy for select patients with T-cell malignancies and an array of inflammatory autoimmune disorders. Finally, therapy with this antibody armed with (90)Y has led to clinical responses in the majority of patients with adult T-cell leukemia. These insights concerning the IL-2/IL-2 receptor system facilitated the development of effective daclizumab antibody therapy for select patients with leukemia/lymphoma.
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PMID:Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. 1753 23

We report a 62-year-old woman with intravascular lymphomatosis (IVL) which presented as subacute encephalopathy. She was admitted to our hospital because of loss of consciousness in the middle of February, 2006. Laboratory tests indicated elevated serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and cerebrospinal fluid protein. Magnetic resonance imaging (MRI) of the brain revealed multiple infarct-like lesions mainly in the white matter. After admission, her consciousness was soon improved, but the inflammatory response did not disappear with any antibiotics or virucides. Her consciousness was not exacerbated, and she was discharged in the middle of March, although the reason for loss of consciousness remained unknown. After discharge she developed an abnormal behavior and mental deterioration, and therefore she was readmitted late in March. On second admission, her consciousness was drowsy. Neurological examinations revealed conjugate deviation of her eyes to the left, left hemiparesis, and generalized hyporeflexia. Laboratory tests showed more elevated CRP than that of the last time, and raised soluble IL-2 receptor (sIL-2R). The repeated MRI of the brain disclosed that initial lesions of the white matter progressively enlarged and increased in number. To make an appropriate diagnosis of the lesions on the brain MRI, the open brain biopsy was performed. Microscopic examination showed that many small vessels were occluded by lymphoma cells (B-lymphocytes) with hemorrhage, and IVL was diagnosed. She was treated with regimens of combined chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). After chemotherapy her consciousness and left hemiparesis were gradually improved and the levels of CRP were normalized. The infarcts-like lesions detected on the brain MRI became reduced and decreased. IVL is a rare disease, and the prognosis is generally poor, with a rapidly fatal outcome, leading to a postmortem diagnosis. In the present report, we successfully treated the patient by rituximab in addition to standard CHOP therapy. Rituximab may play an important role in the treatment of IVL.
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PMID:[Intravascular lymphomatosis manifesting clinically as subacute encephalopathy]. 1854 Mar 79


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