The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Stuart Noble - One of the best experts on this subject based on the ideXlab platform.
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aldesleukin Recombinant Interleukin 2
BioDrugs, 2012Co-Authors: Stuart NobleAbstract:Synopsis Aldesleukin [Recombinant Interleukin-2 (IL-2)] is a biological response modifier which, like endogenous IL-2, has a range of immunomodulatory properties. Although aldesleukin is currently approved only for treatment of renal cell carcinoma, it has been widely used in patients with metastatic melanoma and has been assessed in numerous noncomparative trials in this indication. Durable complete responses have been reported in a small proportion of patients with good performance status who received immunotherapy or chemoimmunotherapy involving aldesleukin in several clinical trials. Overall median survival times of about 10 or 11 months are typical. Combination chemoimmunotherapy involving aldesleukin has produced relatively high response rates (up to 56%), but these are not predictive of increased survival time. Aldesleukin has not been directly compared with standard chemotherapy in randomised studies. The use of continuous intravenous infusion and subcutaneous administration of aldesleukin, together with improved patient selection, has successfully reduced the severity of adverse events produced by the drug (the original intravenous bolus regimen is particularly toxic and often necessitates admission to an intensive care unit). However, the risk/benefit profile of aldesleukin in the treatment of melanoma requires further study, particularly after subcutaneous administration. Thus, aldesleukin has shown modest efficacy in the treatment of metastatic melanoma. Although aldesleukin-containing regimens have produced promising results in many noncomparative trials, their clinical value in comparison with standard chemotherapy remains to be determined in phase HI studies. Until results from such trials are available, clinicians will need to carefully balance the potential benefits of the drug against the risks and likely quality-of-life implications associated with its toxicity in each patient. Current investigations centre on the use of aldesleukin as part of complex biochemotherapy regimens, and results from these trials are awaited with interest.
D Perillo - One of the best experts on this subject based on the ideXlab platform.
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extended continuous infusion low dose Recombinant Interleukin 2 in advanced cancer prolonged immunomodulation without significant toxicity
Journal of Clinical Oncology, 1991Co-Authors: Michael A Caligiuri, Robert J Soiffer, Christopher J L Murray, Thomas R Klumpp, Michael V Seiden, K Cochran, Christine Cameron, L Buchanan, D PerilloAbstract:In previous clinical trials, Recombinant Interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninef...
Robert J Soiffer - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Interleukin 2 infusions and decreased igg2 subclass concentrations see comments
Blood, 1995Co-Authors: Robert J Soiffer, Christopher J L Murray, Jerome Ritz, N R Phillips, D Jacobsohn, S Chartier, Donna M AmbrosinoAbstract:The administration of low doses of Recombinant Interleukin-2 (rIL-2) in vivo to patients with malignant neoplasms has been demonstrated to selectively increase the number of circulating natural killer (NK) cells in these patients. Recent evidence from SCID mouse models suggests that IgG subclass levels can be influenced by the presence and activity of NK cells. Therefore, we sought to examine the effect of rIL- 2 infusions on human serum IgG subclass concentrations. We determined serum IgG subclass concentrations in 27 cancer patients receiving low- dose rIL-2 by daily continuous intravenous infusion. Eleven of these patients had active, metastatic, nonhematologic tumors; 16 patients had received IL-2 when they were in a minimal residual disease state after autologous or allogeneic bone marrow transplantation. Samples obtained before beginning IL-2 therapy and 8 to 10 weeks into therapy were tested. Treatment with IL-2 resulted in an increase in the percentage of CD56+ NK cells from 18% to 54% (P = .0001). A significant decrease in geometric mean IgG2 concentration from 2,017 micrograms/mL to 1,655 micrograms/mL was noted over this time interval (P = .03). Furthermore, the geometric mean IgG2 concentration after treatment was significantly lower than that of healthy controls (P = .026). In contrast, no significant changes in serum IgG1, IgG3, or IgG4 were noted during r- IL2 infusions. Our data suggest that rIL-2 treatment selectively decreases serum IgG2 concentrations. We speculate that increased NK cells mediate downregulation of human serum IgG2.
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extended continuous infusion low dose Recombinant Interleukin 2 in advanced cancer prolonged immunomodulation without significant toxicity
Journal of Clinical Oncology, 1991Co-Authors: Michael A Caligiuri, Robert J Soiffer, Christopher J L Murray, Thomas R Klumpp, Michael V Seiden, K Cochran, Christine Cameron, L Buchanan, D PerilloAbstract:In previous clinical trials, Recombinant Interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninef...
Christopher J L Murray - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Interleukin 2 infusions and decreased igg2 subclass concentrations see comments
Blood, 1995Co-Authors: Robert J Soiffer, Christopher J L Murray, Jerome Ritz, N R Phillips, D Jacobsohn, S Chartier, Donna M AmbrosinoAbstract:The administration of low doses of Recombinant Interleukin-2 (rIL-2) in vivo to patients with malignant neoplasms has been demonstrated to selectively increase the number of circulating natural killer (NK) cells in these patients. Recent evidence from SCID mouse models suggests that IgG subclass levels can be influenced by the presence and activity of NK cells. Therefore, we sought to examine the effect of rIL- 2 infusions on human serum IgG subclass concentrations. We determined serum IgG subclass concentrations in 27 cancer patients receiving low- dose rIL-2 by daily continuous intravenous infusion. Eleven of these patients had active, metastatic, nonhematologic tumors; 16 patients had received IL-2 when they were in a minimal residual disease state after autologous or allogeneic bone marrow transplantation. Samples obtained before beginning IL-2 therapy and 8 to 10 weeks into therapy were tested. Treatment with IL-2 resulted in an increase in the percentage of CD56+ NK cells from 18% to 54% (P = .0001). A significant decrease in geometric mean IgG2 concentration from 2,017 micrograms/mL to 1,655 micrograms/mL was noted over this time interval (P = .03). Furthermore, the geometric mean IgG2 concentration after treatment was significantly lower than that of healthy controls (P = .026). In contrast, no significant changes in serum IgG1, IgG3, or IgG4 were noted during r- IL2 infusions. Our data suggest that rIL-2 treatment selectively decreases serum IgG2 concentrations. We speculate that increased NK cells mediate downregulation of human serum IgG2.
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extended continuous infusion low dose Recombinant Interleukin 2 in advanced cancer prolonged immunomodulation without significant toxicity
Journal of Clinical Oncology, 1991Co-Authors: Michael A Caligiuri, Robert J Soiffer, Christopher J L Murray, Thomas R Klumpp, Michael V Seiden, K Cochran, Christine Cameron, L Buchanan, D PerilloAbstract:In previous clinical trials, Recombinant Interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninef...
Christian Gisselbrecht - One of the best experts on this subject based on the ideXlab platform.
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high dose Recombinant Interleukin 2 in advanced cutaneous t cell lymphoma
Archives of Dermatology, 1995Co-Authors: Jean Pierre Marolleau, M Baccard, B Flageul, M Rybojad, L Laroche, O Verola, Maud Brandely, P Morel, Christian GisselbrechtAbstract:Background and Design: Treatment of cutaneous T-cell lymphoma is still a difficult challenge, once the usual therapies (topical chemotherapy, phototherapy, radiation therapy, and chemotherapy) have proved to be unsuccessful. New therapies, mostly immunotherapies, are currently under investigation. The use of Recombinant Interleukin-2 has already been evaluated in hematopoietic malignancies. We decided to treat patients with advanced cutaneous T-cell lymphoma relapsing or progressing in spite of the usual treatments with high-dose Recombinant Interleukin-2. Seven patients (three with mycosis fungoides, three with Sezary syndrome, and one with nonepidermotropic large-cell cutaneous lymphoma) were included in this open study. They were scheduled to receive Recombinant Interleukin-2 at a dose of 20×106IU/m2per day, administered by continuous infusion during three fortnightly induction cycles and five monthly consolidation cycles. Results: Three complete responses (two responses to mycosis fungoides; one response to large-cell lymphoma) and two partial responses were obtained. The clinical response appeared after the first cycle of treatment in the good responders. The complete responses are still ongoing 33, 28, and 6 months after completion of Recombinant Interleukin-2 therapy and without any further treatment. Sequential immunophenotypic studies showed an increase of the CD1+cells in the dermal infiltrates. No significant modification of natural killer or cytotoxic T cells could be seen. Conclusions: Despite our low number of cases, our results clearly show that some advanced cutaneous T-cell lymphomas can benefit from high-dose Recombinant Interleukin-2 therapy. Further studies are necessary to determine the exact place of Recombinant Interleukin-2 in the therapeutic arsenal of cutaneous T-cell lymphoma. (Arch Dermatol. 1995;131:574-579)