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)

Recent reports suggest that recombinant interleukin-2 may be effective in the treatment of cancer patients with low tumor burden. Considering the poor long-term survival, 11 ovarian cancer patients with minimal residual disease at second-look have so far been selected for rIL-2 intravenous continuous infusion therapy: two induction courses (3 x 10(6) U/m2/day: 120 h + 108 h) followed by three maintenance courses (3 x 10(6) U/m2/day: 120 h) and third-look laparotomy. At present, three patients are still on treatment, three have completed it, and five have discontinued treatment. Sixty-seven per cent of the planned dose was administered in 49 cycles of which 42 (86%) required dose modifications due to hypotension (greater than or equal to grade III) and nephrotoxicity (greater than grade I). CNS and GI toxicity, allergies and fever, even though requiring dose modifications in a few cases, significantly affected patient compliance. The rebound lymphocytosis was clearly dose-related and a significant percentage increase after rIL-2 was detected only for IL-2 receptor positive cells. To date, four patients are evaluable for response after a median follow-up of 7 months, two progressed during the maintenance period, while one CR and one progression were detected in the two patients so far submitted to third-look laparotomy.
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PMID:Recombinant interleukin-2 continuous infusion in ovarian cancer patients with minimal residual disease at second-look. 278 2

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.
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PMID:Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy. 280 69

Ten patients with high-grade non-Hodgkin's lymphoma (HG-NHL) entered a subcutaneous (s.c.) recombinant interleukin 2 (rIL2) trial within 2 months of undergoing autologous bone marrow transplantation (ABMT). Immunological studies, consisting in T- and natural killer (NK)-cell subset assessment, together with functional assays, such as NK activity and CD16-mediated redirected killing assay, were performed before therapy, after 2 weeks, and then monthly. Phenotypic analysis showed a significant increase (p = 0.01) of CD16 and CD56 NK cells, from 12% to 28% and from 17% to 37%, respectively. In particular, the CD56bright NK cell population showed a tenfold increase, while CD56dim NK cells remained unmodified compared with pretreatment values. The expression of IL2 receptors was also studied and a significant increase (p = 0.01) of CD122 (p75)-positive cells from 8% to 30% was found, while no significant increase was observed in CD25 (p55)-positive cells. Furthermore, rIL2 administration led to an increase of NK activity even at the lowest effectors:target ratio and to an increase of CD16-mediated redirected killing assay. These phenotypic and functional modifications lasted throughout the duration of rIL2 therapy and remained after completion of therapy. In addition, none of the ten patients relapsed, and two of them who started IL2 treatment while still showing residual disease experienced a complete disappearance of the disease after 10 and 7 months of therapy, respectively. Our data suggest that infusion of rIL2 s.c. after ABMT is safe, can selectively increase NK cell number and function, and may have a beneficial effect on the minimal residual disease.
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PMID:Low doses of rIL2 after autologous bone marrow transplantation induce a "prolonged" immunostimulation of NK compartment in high-grade non-Hodgkin's lymphomas. 757 23

Autologous transplantation can induce extended remission in some patients with advanced breast cancer and lymphoma yet nearly 80% and 50%, respectively, will ultimately relapse. In vitro studies suggest that activated natural killer cells (NK) mediate lytic activity against breast cancer and lymphoma cell lines. Therefore, immunotherapy with interleukin-2 (IL-2, Amgen) to activate NK may improve long-term disease-free survival when administered in a post-transplant minimal residual disease setting. To determine the feasibility of administering IL-2 and activation of NK post-transplant, twelve patients (6 breast cancer, 6 lymphoma) were enrolled on a phase I dose escalation study after autologous transplantation (median day + 94, range 50-166). IL-2 was self administered at 0.25 x 10(6) (n = 6) or 0.5 x 10(6) (n = 6) U/m2/day subcutaneously for 84 consecutive days. The best tolerated dose was 0.25 x 10(6) U/m2/day (75% of planned doses given vs. 48% at the higher dose). Dose limiting toxicity occurred in 6 patients (n = 2 at 0.25 x 10(6) U/m2/day, n = 4 at 0.5 x 10(6) U/m2/day) consisting of decreased performance status (n = 2), thrombocytopenia (n = 3, 1 at the lower dose), and mild neutropenia (n = 1 at the lower dose). However, all symptoms resolved within a week following discontinuation of IL-2 and no patient required hospitalization. Circulating soluble IL-2 receptor levels were significantly increased in all patients receiving IL-2. Patients receiving at least 28 days of IL-2 exhibited a greater than 10-fold increment in circulating CD56+bright/CD3- NK. Furthermore, lytic function was increased against NK resistant targets, MCF-7 (breast cancer), and Raji (lymphoma). In vivo IL-2 primed NK cells obtained by lymphapheresis were activated in large-scale ex vivo incubation in high dose IL-2 (1,000 U/mL) at high cell density (10 x 10(6)/mL), in gas permeable bags, and using serum-free media. NK lytic function against MCF-7 and Raji targets was further enhanced. We conclude that low dose subcutaneous IL-2 based immunotherapy is feasible, relatively safe, can be administered in an outpatient setting and hypothesize that additional ex vivo incubation in IL-2 may be used to generate NK cells with potent antitumor effects in vivo.
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PMID:Low dose subcutaneous interleukin-2 after autologous transplantation generates sustained in vivo natural killer cell activity. 920 39

We measured the soluble IL-2 receptor alpha (sIL-2R alpha) in sera and in bone marrow of 20 patients with minimal residual hematological malignances, 6 of them with multiple myeloma (MM), 8 with Hodgkin's disease (HD) and 6 with non-Hodgkin's lymphoma (NHL), low grade. Compared to 10 normal individuals, HD and NHL group of patients had in sera significantly increased levels of sIL-2R alpha (252.8 +/- 42.9 versus 1437.2 +/- 1639 and 761.8 +/- 431 U/ml, respectively). After low-dose IL-2 given subcutaneously once daily at a dose of 1.8 x 10(6) U/patient for 3 weeks, additional significant increase in levels of IL-2R alpha was observed in sera and in bone marrow of patients with NHL (761.8 +/- 431 versus 2633 +/- 788 U/ml and 785 +/- 448 versus 2475 +/- 431 U/ml, respectively). The increase of sIL-2R alpha level after IL-2 therapy was also seen in sera and in bone marrow of HD and MM group; however, because of high standard deviation this increase was not statistically significant. We conclude that 1) in comparison to healthy subjects the levels of sIL-2R alpha remained elevated in HD and NHL patients, even at the stage of minimal residual disease (MRD) after intensive chemotherapy or radiotherapy, 2) the levels of sIL-2R alpha which appeared in sera and bone marrow of patients after IL-2 therapy seemed to be dependent on the type of hematological disorders.
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PMID:Detection of soluble IL-2 receptor in the serum and bone marrow of patients with minimal residual hematological malignancies: induction under therapy with IL-2. 943

One of the important approaches for further prolonging remission duration and eradicating minimal residual disease in acute leukemia is immunotherapy. Four kinds of immunotherapy for acute leukemia are under investigation: (1) monoclonal antibodies, among them, Mylotarg (cytotoxic antibiotic calicheamicin linked to CD33 Mab) is given for the treatment of refractory or relapsed acute myeloid leukemia and molecular relapse in acute promyelocytic leukemia with good results, Campath-1H (antiCD52 Mab) is administered in the treatment of prolymphocytic leukemia and Rituximab (anti-CD20 Mab) in B-PLL with high complete remission rates. Other Mabs under preclinical and clinical trials include anti-IL-2 receptor Mab for the treatment of acute T lymphocytic leukemia, anti-220 kD Mab-6G7 for acute leukemias, recombinant immune toxin BL22 (anti-CD22) for hairy cell leukemia and Mabs labeled with radio-isotopes for different types of acute leukemias; (2) adoptive cellular immunotherapy using cytokine-induced killer cell, alloreactive NK cells, allogeneic or autologous leukemic-specific CD8(+) cytotoxic T lymphocytes, and other immune effector cells; (3) cytokines and other immune modulators comprising IL-2, IL-12, GM-CSF, CD40L, FLT-3L and thalidomide and its derivatives; (4) leukemia vaccines of several different formulations including antigen-specific, leukemia cell-based, leukemia antigen-pulsed dendritic cell (DC) and leukemia-derived DC vaccines, the latter two formulations are more attractive. In conclusion, up to now, the most effective example of immunotherapy in acute leukemia is provided by the administration of Mabs, and the majority of other approaches in immunotherapy for acute leukemia although promising, need further studies.
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PMID:[Present status in studying immunotherapy for acute leukemia and its perspective--Editorial]. 1585 71

Hematopoietic malignancies include leukemia, lymphoma and multiple myeloma. These diseases are primarily diagnosed on the basis of morphological features of affected cells, which appear in peripheral blood, bone marrow and lymphoid organs. By taking advantage of the repetitive accessibility of the neoplastic cells within the peripheral blood / and/or bone marrow aspirates, morphological tests are conducted not only for diagnosis but also for evaluation of clinical outcomes and prognosis, suggesting that the morphological features are considered as a clinical biomarker in hematopoietic malignancies. However, remarkable progress in molecular targeted therapy and allogeneic hematopoietic stem cell transplantation has improved the long-term prognosis of patients with hematopoietic malignancies, and some patients are curable. Under such modern strategies for therapy, monitoring of minimal residual disease(MRD), which is morphologically undetectable, is required to guide proper management of the disease by evaluation of an optimal response to therapy and early detection of disease relapse. At present, both immunophenotypes(surface markers)and chimeric fusion genes(e. g. BCR-ABL in chronic myeloid leukemia)characteristic of hematopoietic malignant cells are analyzed as clinically useful biomarkers to monitor MRD by two highly sensitive methods, multiparameter flow cytometry and real-time quantitative PCR, respectively. On the other hand, serum markers reflecting the size of the tumor mass are clinically available to monitor the disease progression in mass-forming hematopoietic malignancies: e. g., soluble IL-2 receptor for lymphoma and M-protein or free light chain for multiple myeloma.
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PMID:[Clinical values of biomarkers in hematopoietic malignancies]. 1915 62

Hematopoietic malignancies, including leukemia, lymphoma and multiple myeloma, are classified and predicted a prognosis by morphologic, cytogenetic and molecular features. With advances in molecular targeted therapy and hematopoietic stem cell transplantation, monitoring of minimal residual disease (MRD) is required for evaluation of an optimal response to therapy and early detection of disease relapse. Analysis of immunophenotypes and chimeric fusion genes characteristic for hematopoietic malignant cells are clinically useful biomarkers to classify into subtype at diagnosis and monitor MRD. On the other hand, serum markers reflecting tumor burden are clinically useful to monitor the disease progression in hematopoietic malignancies: e.g., LDH and soluble IL-2 receptor for lymphoma; M-protein and free light chain for multiple myeloma.
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PMID:[Hematopoietic malignancy (leukemia, malignant lymphoma, multiple myeloma)]. 2262 9