The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Lanny J Rosenwasser - One of the best experts on this subject based on the ideXlab platform.
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anti cd23 monoclonal antibody Lumiliximab inhibited allergen induced responses in antigen presenting cells and t cells from atopic subjects
The Journal of Allergy and Clinical Immunology, 2005Co-Authors: Jill A Poole, Jianfeng Meng, Mitchell Reff, Mary C Spellman, Lanny J RosenwasserAbstract:Background CD23 plays a role in the regulation of IgE production and allergy-induced immune and inflammatory responses. A novel anti-CD23 monoclonal antibody, Lumiliximab, is a potential therapeutic antibody recently demonstrated to be safe in human beings. Objective This study investigated the effects of Lumiliximab on allergen-induced immune responses from atopic subjects compared with blocking HLA-DR and costimulatory molecules, CD80 and CD86. Methods Allergen-stimulated PBMCs from atopic subjects were pretreated with Lumiliximab or antibodies to CD80, CD86, and HLA-DR. Cultures were analyzed for cell proliferation and IL-1β, TNF-α, and IL-5 cytokine secretion. An allergen-specific T-cell line was developed and analyzed for lymphocyte proliferation in response to allergen with or without Lumiliximab. Lumiliximab's effect on CD86 expression was evaluated by flow cytometry in the U937 monocytic cell line. Results Lumiliximab reduced allergen-induced PBMC proliferation by 50% (n = 6; P = .006). In addition, cultures pretreated with Lumiliximab had a reduction in the proinflammatory cytokines IL-1β ( P P = .05) and the T H 2 cytokine IL-5 ( P = .002). Blocking CD86 resulted in greater reduction in proliferation than Lumiliximab ( P = .003) but similar effects in cytokine secretion. The anti-CD80 blocking antibody had no effect on cytokine production but did reduce proliferation. Furthermore, the addition of Lumiliximab to cytokine stimulated U937 cells reduced surface expression of CD86 ( P = .012). Conclusion These results indicate that the anti-CD23 mAb, Lumiliximab, may be involved in modulating antigen presenting cells and reducing T H 2-type immune responses. The use of this antibody may provide clinical benefit for treating allergic diseases.
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anti cd23
2005Co-Authors: Lanny J Rosenwasser, Jianfeng MengAbstract:CD23, the low-affinity immunoglobulin (Ig)E receptor (FceRII), is widely distributed on the surface of various human cells. CD23 mediates numerous IgE-related immune responses (including allergen focusing) by enhancing IgE antigen complex presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells, and stimulating production of pro-inflammatory mediators from monocytes/macrophages, eosinophils, and even airway smooth muscle cells. Both membrane and soluble CD23 play an important role in allergic reactions. Cellular contacts and cytokines modulate its expression in a concerted manner as needed for allergic reactions. Expression of CD23 and soluble CD23 has been associated with allergic diseases. Targeting CD23 with monoclonal antibody (MAb) is a promising candidate therapy in allergic diseases. A newly developed agent known as Lumiliximab, which is an anti-CD23 MAb (Lumiliximab), was demonstrated to be a well-tolerated agent in a phase I clinical trial (a placebo-controlled study with allergic asthma). Adverse events were mild, and no relationship was apparent between the dose of Lumilixilab and the frequency, severity, or type of event. Sustained and dose-dependent decreases in mean serum total IgE concentrations were noted. The serum half-life of Lumilixilab increased from 2 to 10 d with increasing doses. Blocking antigen presentation, preventing costimulation signals, and reducing production of pro-inflammatory mediators are some of the potential mechanisms involved for anti-CD23 activity. Although the safety and clinical efficacy of Lumilixilab in allergic asthma and rhinitis require confirmation, the observed data imply that anti-CD23 is a promising candidate therapy option for future treatment of allergic diseases.
Awan, Farrukh T - One of the best experts on this subject based on the ideXlab platform.
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A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of Lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.
'Wiley', 2014Co-Authors: Awan, Farrukh T, Hillmen Peter, Hellmann Andrzej, Robak Tadeusz, Hughes, Steven G, Trone Denise, Shannon Megan, Flinn, Ian W, Byrd, John C, Lucid Trial InvestigatorsAbstract:Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with Lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of Lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of Lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without Lumiliximab). There was a slightly increased incidence of adverse events with Lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of Lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL
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A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of Lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia
'Wiley', 2014Co-Authors: Awan, Farrukh T, Bron DominiqueAbstract:Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with Lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of Lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of Lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without Lumiliximab). There was a slightly increased incidence of adverse events with Lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of Lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.0SCOPUS: ar.jSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe
Jianfeng Meng - One of the best experts on this subject based on the ideXlab platform.
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anti cd23 monoclonal antibody Lumiliximab inhibited allergen induced responses in antigen presenting cells and t cells from atopic subjects
The Journal of Allergy and Clinical Immunology, 2005Co-Authors: Jill A Poole, Jianfeng Meng, Mitchell Reff, Mary C Spellman, Lanny J RosenwasserAbstract:Background CD23 plays a role in the regulation of IgE production and allergy-induced immune and inflammatory responses. A novel anti-CD23 monoclonal antibody, Lumiliximab, is a potential therapeutic antibody recently demonstrated to be safe in human beings. Objective This study investigated the effects of Lumiliximab on allergen-induced immune responses from atopic subjects compared with blocking HLA-DR and costimulatory molecules, CD80 and CD86. Methods Allergen-stimulated PBMCs from atopic subjects were pretreated with Lumiliximab or antibodies to CD80, CD86, and HLA-DR. Cultures were analyzed for cell proliferation and IL-1β, TNF-α, and IL-5 cytokine secretion. An allergen-specific T-cell line was developed and analyzed for lymphocyte proliferation in response to allergen with or without Lumiliximab. Lumiliximab's effect on CD86 expression was evaluated by flow cytometry in the U937 monocytic cell line. Results Lumiliximab reduced allergen-induced PBMC proliferation by 50% (n = 6; P = .006). In addition, cultures pretreated with Lumiliximab had a reduction in the proinflammatory cytokines IL-1β ( P P = .05) and the T H 2 cytokine IL-5 ( P = .002). Blocking CD86 resulted in greater reduction in proliferation than Lumiliximab ( P = .003) but similar effects in cytokine secretion. The anti-CD80 blocking antibody had no effect on cytokine production but did reduce proliferation. Furthermore, the addition of Lumiliximab to cytokine stimulated U937 cells reduced surface expression of CD86 ( P = .012). Conclusion These results indicate that the anti-CD23 mAb, Lumiliximab, may be involved in modulating antigen presenting cells and reducing T H 2-type immune responses. The use of this antibody may provide clinical benefit for treating allergic diseases.
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anti cd23
2005Co-Authors: Lanny J Rosenwasser, Jianfeng MengAbstract:CD23, the low-affinity immunoglobulin (Ig)E receptor (FceRII), is widely distributed on the surface of various human cells. CD23 mediates numerous IgE-related immune responses (including allergen focusing) by enhancing IgE antigen complex presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells, and stimulating production of pro-inflammatory mediators from monocytes/macrophages, eosinophils, and even airway smooth muscle cells. Both membrane and soluble CD23 play an important role in allergic reactions. Cellular contacts and cytokines modulate its expression in a concerted manner as needed for allergic reactions. Expression of CD23 and soluble CD23 has been associated with allergic diseases. Targeting CD23 with monoclonal antibody (MAb) is a promising candidate therapy in allergic diseases. A newly developed agent known as Lumiliximab, which is an anti-CD23 MAb (Lumiliximab), was demonstrated to be a well-tolerated agent in a phase I clinical trial (a placebo-controlled study with allergic asthma). Adverse events were mild, and no relationship was apparent between the dose of Lumilixilab and the frequency, severity, or type of event. Sustained and dose-dependent decreases in mean serum total IgE concentrations were noted. The serum half-life of Lumilixilab increased from 2 to 10 d with increasing doses. Blocking antigen presentation, preventing costimulation signals, and reducing production of pro-inflammatory mediators are some of the potential mechanisms involved for anti-CD23 activity. Although the safety and clinical efficacy of Lumilixilab in allergic asthma and rhinitis require confirmation, the observed data imply that anti-CD23 is a promising candidate therapy option for future treatment of allergic diseases.
Byrd, John C - One of the best experts on this subject based on the ideXlab platform.
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A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of Lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.
'Wiley', 2014Co-Authors: Awan, Farrukh T, Hillmen Peter, Hellmann Andrzej, Robak Tadeusz, Hughes, Steven G, Trone Denise, Shannon Megan, Flinn, Ian W, Byrd, John C, Lucid Trial InvestigatorsAbstract:Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with Lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of Lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of Lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without Lumiliximab). There was a slightly increased incidence of adverse events with Lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of Lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL
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Phase 1/2 study of Lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia
American Society of Hematology, 2024Co-Authors: Byrd, John C, Flinn, Ian W, Kipps, Thomas J., Castro Januaro, Lin, Thomas S., Wierda William, Heerema Nyla, Woodworth James, Hughes Steve, Tangri ShabnamAbstract:Preclinical data demonstrate enhanced antitumor effect when Lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with Lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose-escalation study of Lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m2 (n = 3) or 500 mg/m2 (n = 28) of Lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a complete response (CR), which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL. The estimated median progression-free survival for all responders was 28.7 months. The addition of Lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not appear to enhance toxicity in previously treated patients with CLL. A randomized trial comparing Lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL. This trial was registered at clinicaltrials.gov as NCT00103558
Flinn, Ian W - One of the best experts on this subject based on the ideXlab platform.
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A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of Lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.
'Wiley', 2014Co-Authors: Awan, Farrukh T, Hillmen Peter, Hellmann Andrzej, Robak Tadeusz, Hughes, Steven G, Trone Denise, Shannon Megan, Flinn, Ian W, Byrd, John C, Lucid Trial InvestigatorsAbstract:Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with Lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of Lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of Lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without Lumiliximab). There was a slightly increased incidence of adverse events with Lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of Lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL
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Phase 1/2 study of Lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia
American Society of Hematology, 2024Co-Authors: Byrd, John C, Flinn, Ian W, Kipps, Thomas J., Castro Januaro, Lin, Thomas S., Wierda William, Heerema Nyla, Woodworth James, Hughes Steve, Tangri ShabnamAbstract:Preclinical data demonstrate enhanced antitumor effect when Lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with Lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose-escalation study of Lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m2 (n = 3) or 500 mg/m2 (n = 28) of Lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a complete response (CR), which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL. The estimated median progression-free survival for all responders was 28.7 months. The addition of Lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not appear to enhance toxicity in previously treated patients with CLL. A randomized trial comparing Lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL. This trial was registered at clinicaltrials.gov as NCT00103558
