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)

Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell induction. The target cells utilized for assay were a human leukemia cell line K562, a human renal carcinoma cell line KU-2, autologous normal kidney tissues and autologous renal cell carcinomas. Culture supernatant of peripheral blood lymphocytes (PBL) and OK-432 (designated as OK conditioned medium or OK-CM) demonstrated enhanced cytotoxicity of fresh PBL against these target cells. Killer cell activity against autologous cancer cells could be also induced from PBL of renal cell carcinoma patients. Pretreatment of PBL with IFN-gamma revealed synergistic effect of OK-CM on killer cell induction. OK-CM derived from patients was shown to contain IL-2 activity as well as high titer of interferon. Neutralizing monoclonal antibody against IFN-gamma and IL-2 receptor demonstrated reduction of cytotoxicity. These results suggested potential benefit of sequential use of IFN-gamma and OK-432 for the treatment of metastatic renal cell carcinoma.
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PMID:Combination therapy for renal cell carcinoma using IFN-gamma and OK-432: in vitro study. 211 48

Human autologous peripheral blood lymphocytes (PBL) and lymphocytes infiltrating renal cell carcinoma (TIL) were cultured with medium containing 1000 IU/ml of human interleukin 2 (IL-2). A high cytotoxic activity against fresh autologous as well as cultured allogenic tumor cells was developed. By culturing these lymphocytes with OKT3 monoclonal antibody during the initial 2 days of long-term culture, in terms of T cell activation signal, IL-2-driven lymphocyte proliferation was remarkably accelerated with maintenance of appreciable level of cytotoxic activity. The same culture method also induced an increase in OKT3 and IL-2 receptor positive lymphocyte population in LAK cells and TIL. This method may enable us to gain more autologous TIL in vitro for adoptive immunotherapy of renal cell carcinoma than the usual culture method with IL-2 alone. Five patients with metastatic renal cell carcinoma were treated with adoptive immunotherapy with TIL, LAK and IL-2. One patient with pulmonary metastasis has had a minor response which has lasted for 3 months so far. We have not experienced any serious side effects during the treatment.
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PMID:[Study on adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) for renal cell carcinoma--amplification of IL-2-elicited TIL proliferation by OKT3-monoclonal antibody]. 230 7

The purpose of this study was to compare the toxicity, immunomodulatory changes, and antitumor efficacy of interleukin 2 (IL-2) and lymphokine activated killer (LAK) cell therapy with two durations of IL-2 infusion. Patients with progressive melanoma, non-Hodgkin's lymphoma, renal carcinoma, or colon carcinoma received IL-2 at 3 X 10(6) units/m2/day on days 1-5 and 13-17, either by bolus injection every 8 h (q8h) or by continuous i.v. (CIV) administration. Peripheral blood mononuclear cells were harvested by leukapheresis on days 8, 9, and 10, were incubated in vitro for 5 days for generation of LAK cells, and were infused on days 13, 14, and 15. The first 11 patients were treated with IL-2 q8h, and the subsequent 13 patients were treated by CIV infusion. Toxicity consisted primarily of fever, chills, emesis, diarrhea, weight gain, and edema but did not require intensive care unit support and did not differ significantly between treatment groups. IL-2-induced lymphocytosis on day 8 was higher with CIV than with q8h administration with a mean lymphocyte count/microliter of 5610 +/- 700 (SE) versus 3300 +/- 500. Immunomodulatory changes observed on days 8 and 20 were also greater with CIV IL-2 and included an increase in peripheral blood mononuclear cell IL-2 receptor expression as well as a marked rise in the number of Leu-11+ and Leu-19+ peripheral blood mononuclear cells. The total leukapheresis yield per patient and total number of LAK cells infused per patient were higher with CIV than q8h administration, with 49.8 +/- 4.9 X 10(9) versus 39.4 +/- 5.4 X 10(9) and 42.6 +/- 5.0 X 10(9) versus 34.0 +/- 5.4 X 10(9), respectively. The cells infused displayed phenotypic evidence of activation and exhibited marked lytic reactivity to Daudi, Raji, and HT-144 targets. One complete and one minimal response were observed in 2 of 8 patients with metastatic renal cell carcinoma who received CIV IL-2 and LAK cells. The results show that IL-2 is more biologically active by CIV than q8h administration, as demonstrated by greater rebound lymphocytosis, LAK cell yield, and in vivo immunostimulation.
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PMID:Influence of schedule of interleukin 2 administration on therapy with interleukin 2 and lymphokine activated killer cells. 278 43

Elevated serum levels of soluble tumour necrosis factor receptor (sTNFR-55) and (at a lesser degree) of sTNFR-75 were found in most of the patients with metastatic renal cell carcinoma (RCC) or malignant melanoma (MM) before immunotherapy and with further increase during treatment (intravenous infusions of interleukin-2 [IL-2] and subcutaneous interferon-alpha [IFN-alpha]). In the majority of the patients with MM the pretreatment serum levels of IL-2 and soluble IL-2 receptor (sIL-2R) were increased, whereas fewer patients with RCC presented with increased serum levels of IL-2 and sIL-2R. Twelve days' treatment with IL-2/IFN-alpha, with a rest on days 6 and 7, resulted in a consistent further increase in the serum levels of sIL-2R and sTNFRs. In most patients the increase of sIL-2R and sTNFRs lasted for at least 3 weeks after treatment discontinuation. The clinical significance of the increase remains unknown.
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PMID:Serum levels of cytokines and soluble cytokine receptors in patients with metastatic renal cell carcinoma or malignant melanoma receiving IL-2/interferon-alpha combination therapy. 754 24

Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-alpha, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-alpha at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-alpha was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreatment using rIL-2, rIL-2 and rIFN-alpha, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific to rIL-2.
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PMID:Low-dose interleukin-2 in combination with interferon-alpha effectively modulates biological response in vivo. 768 66

Recombinant interleukin-2 (IL-2) products (e.g. aldesleukin, teceleukin) are nonglycosylated, modified forms of the endogenous compound. IL-2 acts as a pleiotropic mediator within the immune system, having a variety of effects via specific cell surface receptors. The interaction of IL-2 with the IL-2 receptor induces proliferation and differentiation of a number of T lymphocyte subsets, and stimulates a cytokine cascade that includes various interleukins, interferons and tumour necrosis factors. Antitumour effects of IL-2 appear to be mediated by its effects on natural killer, lymphokine-activated killer (LAK) and other cytotoxic cells. In vivo and in vitro effects of IL-2 seem to be dependent to a large extent on the environment; many studies have reported conflicting results, perhaps due to diverse populations of effector cells, the availability of other cytokines that have synergistic or inhibitory influences, and the dosage regimens used. The recombinant products appear to be biologically indistinguishable from native IL-2 in vitro and in vivo; the former induce minor antibody formation but this does not appear to alter functional properties. In patients with metastatic renal cell carcinoma, IL-2 therapy achieves average objective response rates of 20% (range 0 to 40%), with a complete response rate of about 5% (range 0 to 19%). Response duration varies considerably but can be durable (lasting for > 12 months), with some patients remaining in complete response for > 60 months. It is unclear at present whether higher dosage regimens improve clinical response, or whether combination therapy with other agents and/or adoptive therapy is beneficial. Survival duration may depend on the risk factors present, with poorer performance status and more than one site of metastases associated with shorter survival times. Patients with metastatic malignant melanoma receiving IL-2 as monotherapy show an average objective response rate of 13% (range 3 to 24%); however, objective response rate averages 30% (range 4 to 59%) when IL-2 is used in combination with other agents. Overall median survival appears to be about 10 months. Preliminary data indicate that IL-2 produces a lower response rate in patients with refractory colorectal carcinoma, ovarian cancer, bladder cancer, acute myeloid leukemia or non-Hodgkin's lymphoma. Adverse effects accompanying high dose, intravenous IL-2 therapy can be severe, with cardiovascular, pulmonary, haematological, hepatic, neurological, endocrine, renal and/or dermatological complications frequently requiring doses to be withheld.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. 769 34

Interleukin-1 (IL-1) plays a central role in the immune system, partly by stimulating the production of interleukin-2 (IL-2) and other cytokines by lymphocytes. In preclinical studies, recombinant interleukin-1 (rIL-1 beta) has shown antitumor activity. We conducted a phase II trial to evaluate the efficacy of rIL-1 in metastatic renal cell carcinoma (RCC). rIL-1 beta was given at a dose of 50 ng/kg i.v. daily for 5 days on a 28-day schedule. Nineteen patients were registered; 16 completed two cycles and were evaluable for response. There were no complete or partial responses to treatment. Toxicity was generally mild and typically involved grades I and II fever, rigors, hypotension, and weight gain. Severe neurologic toxicity was seen in two patients, grade IV seizures were seen in one, and grade III somnolence was seen in another. Analysis of soluble IL-2 receptor (sIL-2r) levels revealed an increase from a mean pretreatment level of 4,567 pg/ml to a mean of 6,124 pg/ml posttreatment (p < 0.001). The mean pretreatment IL-6 level was 51 pg/ml, increased to 84 pg/ml posttreatment (p < 0.05). Patients with bulky disease had higher sIL-2r levels, and patients with tumor fevers had higher IL-6 and sIL-2r levels than patients without fever did. A neutrophilic leukocytosis and a mild thrombocytosis were observed in response to rIL-1 beta administration. We conclude that rIL-1 beta in this dose and schedule is inactive in metastatic RCC.
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PMID:Phase II trial of recombinant interleukin-1 beta in patients with metastatic renal cell carcinoma. 783 20

A patient with longstanding scleroderma with myositis was treated with interleukin 2 (IL-2) and lymphokine activated killer (LAK) cells for locally metastatic renal cell carcinoma. A rapid progression of truncal skin thickening and muscle weakness occurred within weeks of the initial infusion. Studies using supernatants from peripheral T lymphocytes of patients with scleroderma have shown increased levels of IL-2, IL-2 receptor, IL-4 and B cell growth factors, indications of activation of immune mechanisms. The rapid progression of our patient's illness during immunotherapy suggests a primary role for IL-2 and LAK cells in this disorder. Patients with scleroderma who receive IL-2 and LAK cells should be monitored prospectively for exacerbation of their illness.
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PMID:Rapid exacerbation of scleroderma in a patient treated with interleukin 2 and lymphokine activated killer cells for renal cell carcinoma. 859 71

We evaluated adoptive immunotherapy using LAK cells combined with systemic administration of interleukin-2 (IL-2) in 11 patients with metastatic renal cell carcinoma. The LAK cells were generated by incubation in serum-free medium (AIM-V) supplemented with IL-2 (1,000 U/ml) for 4 days and were generally administered twice weekly (4 times/cycle). Daily administration of IL-2 (50 x 10(5) U) was started 3 days prior to the first LAK infusion and continued throughout the cycle. Each course of therapy comprised 1-6 cycles, with the total dose of LAK cells and IL-2 varying from 3.3-52.6 x 10(9) cells and 140-900 x 10(5) U, respectively. Clinical response was evaluated in terms of metastasis to specific organs (lung only: eight cases, lung and brain: one, lung and lymph nodes: one, lung and bone and pleuropericardium: one). The outcome was complete response in one patient, partial response in one, no change in six and disease progression in three. The response rate was 18.8%. This therapy was most effective against pulmonary metastases. Adverse reactions to LAK cell infusion included fever, headache, and chills. Eosinophilia and weight gain due to IL-2 administration were also observed. However, all of these symptoms were transient and no serious side effects occurred. In these patients, the proportion of natural killer (NK) cells (CD16) and cells with IL-2 receptor (CD25) among PBL was increased markedly in the early phase of therapy, and activated T cell (CD3+DR+) and suppressor T cells (CD8+11+) increased significantly at a later phase. It was suggested that the clinical response would be expected in case of increasing of CD16 cells or CD25 cells and augmentation of NK or LAK activity. Our results indicate that this regimen of adoptive immunotherapy shows some promise for the treatment of advanced renal cell carcinoma.
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PMID:[Study of adoptive immunotherapy for metastatic renal cell carcinoma with lymphokine-activated killer (LAK) cells and interleukin-2. II. Clinical evaluation]. 832 Aug 88

In addition to IL-2, IL-12 would constitute one of the most promising cytokines in the treatment of human neoplasms. IL-2 has been proven to induce in vitro and in vivo several evident changes in the secretion of cytokines and various other immunoinflammatory substances. In contrast, very little data are available about the immune effects of IL-12 in humans. The present study was carried out to investigate the in vivo immunoinflammatory effects of IL-12 by analyzing the secretions of neopterin, soluble IL-2 receptor (SIL-2R), tumor necrosis factor alpha (TNF), IL-2 and IL-6 in relation to the neuroendocrine function of the pineal gland, which is one of the most important organs involved in neuroimmunomodulation. Pineal endocrine function was investigated by evaluating the whole daily urinary excretion of the main catabolite of its hormone melatonin, 6-sulfatoxymelatonin (6-MTS). The study was performed on metastatic renal cell cancer patients. Each course of IL-12 consisted of 1.25 microg/ kg b.w. subcutaneously in the morning once a week for 3 consecutive weeks. The study evaluated 10 IL-12 courses. Mean serum levels of neopterin, SIL-2R and TNF significantly increased in response to IL-12, whereas no significant change occurred in IL-6 and IL-2 mean concentrations. Finally, 6-MTS urinary excretion was significantly reduced by IL-12 injection, particularly during the dark phase of the day. This preliminary study would suggest that IL-12 may induce important changes in the in vivo immunoinflammatory response. Moreover, IL-12 administration would suppress pineal endocrine activity, thus confirming its previously suggested involvement in the neuroimmunomodulatory processes. Because of the fundamental role of the pineal gland in neuroimmunomodulation, IL-12-induced immune variations could depend at least in part on its action at central neuroendocrine sites.
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PMID:Immunomodulatory effects of IL-12 in relation to the pineal endocrine function in metastatic cancer patients. 1106 86


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