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Dale G Renlund - One of the best experts on this subject based on the ideXlab platform.
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the repetitive histologic pattern of vascular cardiac allograft rejection increased incidence associated with longer exposure to prophylactic murine monoclonal anti CD3 Antibody okt3
Transplantation, 1996Co-Authors: Elizabeth H Hammond, Michael R Bristow, John B Oconnell, Robert L Yowell, David O Taylor, Dale G RenlundAbstract:While vascular cardiac allograft rejection increases morbidity and mortality following transplantation, factors predisposing to its development have not been completely elucidated. To evaluate the influence of the duration of early rejection prophylaxis with the murine monoclonal anti-CD3 Antibody (
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the repetitive histologic pattern of vascular cardiac allograft rejection increased incidence associated with longer exposure to prophylactic murine monoclonal anti CD3 Antibody okt3
Transplantation, 1996Co-Authors: Elizabeth H Hammond, Michael R Bristow, John B Oconnell, David O Taylor, R L Yowell, Dale G RenlundAbstract:While vascular cardiac allograft rejection increases morbidity and mortality following transplantation, factors predisposing to its development have not been completely elucidated. To evaluate the influence of the duration of early rejection prophylaxis with the murine monoclonal anti-CD3 Antibody (OKT3) on the development of a repetitive histologic pattern of vascular cardiac allograft rejection, endomyocardial biopsies from 344 heart transplant recipients were prospectively evaluated. The influence of clinical characteristics was assessed. Eighty-three patients (24%) developed and 261 patients (76%) did not develop a repetitive histologic pattern of vascular cardiac allograft rejection. The vascular rejection pattern was more common in patients with a positive crossmatch (89% versus 11%, P<0.0001) and OKT3 sensitization (73% versus 27%, P<0.0001), and was positively correlated with the duration of OKT3 treatment (P<0.0001). The correlation persists even after excluding patients with a positive crossmatch or OKT3 sensitization. Patients developing a repetitive histologic pattern of vascular cardiac allograft rejection early after transplantation had decreased allograft survival (P=0.0008). The development of a repetitive histologic pattern of vascular cardiac allograft rejection is positively correlated with the duration of OKT3 treatment. Judicious use of OKT3 in early rejection prophylaxis in cardiac transplantation is warranted.
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prevention of adverse clinical outcome by monitoring of cardiac transplant patients for murine monoclonal CD3 Antibody okt3 sensitization
Transplantation, 1993Co-Authors: Elizabeth Hammond, Dale G Renlund, Robert L Yowell, Jay Greenwood, Leha Hartung, Carl T WittwerAbstract:We have previoulsy reported that patients sensitized to murine monoclonal CD3 Antibody (OKT3) and maintained on such therapy for induction of immunosuppression have a high mortality and/or allograft loss. In this follow-up study, we retrospectively reviewed all patients routinely and serially monitored by flow cytometry for plasma levels of OKT3 during a 21-month period begining 1/90. A total of 112 patients were monitored during this period
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murine monoclonal CD3 Antibody okt3 based early rejection prophylaxis in pediatric heart transplantation
Journal of Heart and Lung Transplantation, 1993Co-Authors: Robert E Shaddy, Dale G Renlund, Emily A Bullock, N J Morwessel, D W Hannon, S V Karwande, Edwin C Mcgough, John A HawkinsAbstract:: The purpose of this study was to review our experience with the use of OKT3 (a murine monoclonal CD3 Antibody) used as immune prophylaxis for pediatric heart transplant recipients. Orthotopic heart transplantation was performed in 18 pediatric patients, 8 girls and 10 boys, ranging in age from 17 days to 17 years. OKT3 therapy was initiated intraoperatively at a dose of approximately 0.2 mg/kg and was administered at a dose of approximately 0.1 to 0.2 mg/kg/day for a period of 11.5 +/- 2.5 days. Daily average OKT3 levels were 1132 +/- 469 ng/ml. Side effects that occurred during OKT3 therapy were fever (59%), diarrhea (24%), headaches (24%), vomiting (18%), encephalopathy (12%), pulmonary edema (6%), and rash (6%). Infections occurred in 24% of patients, all within 6 months of transplantation. In the first year after transplantation, patients experienced 3.4 +/- 2.4 episodes of mild rejection and 1.0 +/- 0.8 episodes of moderate rejection. No patient experienced severe rejection. Five of the surviving 14 patients (36%) have been weaned from chronic steroid therapy, and 42% are being maintained on alternate-day prednisone at a dose of 0.06 +/- 0.02 mg/kg/day. Coronary artery disease developed in three patients; two of whom died. Actuarial survival was 83% at 1 year and 73% at 2 years. This report shows that OKT3 prophylaxis in pediatric heart transplantation can be used with acceptable short-term adverse side effects and overall survival.
Paul A Carpenter - One of the best experts on this subject based on the ideXlab platform.
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a phase ii multicenter study of visilizumab humanized anti CD3 Antibody to treat steroid refractory acute graft versus host disease
Biology of Blood and Marrow Transplantation, 2005Co-Authors: Paul A Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, H Khoury, Pablo Parker, Keith R Jerome, Jeannine S MccuneAbstract:Abstract Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal Antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
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a humanized non fcr binding anti CD3 Antibody visilizumab for treatment of steroid refractory acute graft versus host disease
Blood, 2002Co-Authors: Paul A Carpenter, Paul J. Martin, F R Appelbaum, K Doney, Lawrence Corey, Joachim H Deeg, Ted Gooley, James Krueger, Sandra Pavlovic, J E SandersAbstract:Visilizumab is a humanized anti-CD3 monoclonal Antibody characterized by a mutated IgG2 isotype, lack of binding to Fcγ-receptors, and ability to induce apoptosis selectively in activated T cells. To test pharmacokinetics, safety, and immunosuppressive activity of visilizumab, 17 patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD) were enrolled in a phase 1 study. Six patients were given 7 doses of visilizumab (0.25 or 1.0 mg/m2) on days 1, 3, 5, 7, 9, 11, and 13. Because multiple doses of 1 mg/m2 caused delayed visilizumab accumulation and prolonged lymphopenia, the next 11 patients received a single dose of 3.0 mg/m2 on day 1. GVHD improved in all patients; 15 were evaluable through day 42. Multiple dosing resulted in 1 of 6 complete responses (CRs) and 5 partial responses (PRs), but all 6 patients died at a median of 87 days after starting visilizumab therapy. Single dosing resulted in 6 of 9 CRs, 3 PRs, and 7 of 11 patients surviving after 260 to 490 days (median, 359 days; P = .03). There were no allergic reactions and 3 grade 1 acute infusional toxicities. Plasma Epstein-Barr virus (EBV) DNA titers more than 1000 copies/mL and posttransplant lymphoproliferative disease (PTLD) developed in 2 of the first 7 patients. Based on rising EBV DNA titers, 5 of the next 10 patients were given the B cell–specific monoclonal Antibody, rituximab. EBV DNA became undetectable and no overt PTLD developed. Visilizumab is well tolerated and has activity in advanced GVHD. A phase 2 study incorporating preemptive therapy for PTLD is warranted to determine the efficacy of visilizumab in GVHD.
Niels Junker - One of the best experts on this subject based on the ideXlab platform.
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preclinical development of tumor infiltrating lymphocyte til based adoptive cell transfer act immunotherapy for patients with sarcoma and the potential benefit of anti cd137 stimulation
Journal of Clinical Oncology, 2017Co-Authors: Morten Nielsen, Anders Kraruphansen, Dorrit Hovgaard, Michael Mork Petersen, Anand C Loya, Marie Christine Wulff Westergaard, Inge Marie Svane, Niels JunkerAbstract:e14545Background: Tumor specific TILs can be in vitro expanded and have the ability to induce complete and durable tumor regression in some patients following ACT. In this preclinical study we investigated the feasibility of expanding TILs from sarcomas, as well as performing functional in vitro analyses on these. Methods: Fresh tumor samples from sarcoma patients were obtained, and TILs were isolated and expanded in growth medium containing IL-2. In a sub study, we investigated the effect of adding an agonistic CD137 Antibody (Urelumab, BMS) and/or an anti-CD3 Antibody (OKT3) to the medium. Phenotype and functional analyses was performed using flow cytometry and IFNγ-Elispot. Results: Tumor samples from 30 patients with various types of sarcomas were obtained, and we were able to expand a minimum of 40 million TILs from 27 of these. Mean expansion times were 32 days (14 - 61). 87,7 % (36,4 – 99,1) of these cells were CD3+, and of these, 66,7 % (16,3 – 99,1) were CD4+, and 21,8 % (0,1 – 50,6) were CD8+. A...
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Preclinical development of tumor-infiltrating lymphocyte (TIL) based adoptive cell transfer (ACT) immunotherapy for patients with sarcoma and the potential benefit of anti-CD137 stimulation.
Journal of Clinical Oncology, 2017Co-Authors: Morten Nielsen, Dorrit Hovgaard, Michael Mork Petersen, Anand C Loya, Marie Christine Wulff Westergaard, Inge Marie Svane, Anders Krarup-hansen, Niels JunkerAbstract:e14545Background: Tumor specific TILs can be in vitro expanded and have the ability to induce complete and durable tumor regression in some patients following ACT. In this preclinical study we investigated the feasibility of expanding TILs from sarcomas, as well as performing functional in vitro analyses on these. Methods: Fresh tumor samples from sarcoma patients were obtained, and TILs were isolated and expanded in growth medium containing IL-2. In a sub study, we investigated the effect of adding an agonistic CD137 Antibody (Urelumab, BMS) and/or an anti-CD3 Antibody (OKT3) to the medium. Phenotype and functional analyses was performed using flow cytometry and IFNγ-Elispot. Results: Tumor samples from 30 patients with various types of sarcomas were obtained, and we were able to expand a minimum of 40 million TILs from 27 of these. Mean expansion times were 32 days (14 - 61). 87,7 % (36,4 – 99,1) of these cells were CD3+, and of these, 66,7 % (16,3 – 99,1) were CD4+, and 21,8 % (0,1 – 50,6) were CD8+. A...
Jeannine S Mccune - One of the best experts on this subject based on the ideXlab platform.
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a phase ii multicenter study of visilizumab humanized anti CD3 Antibody to treat steroid refractory acute graft versus host disease
Biology of Blood and Marrow Transplantation, 2005Co-Authors: Paul A Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, H Khoury, Pablo Parker, Keith R Jerome, Jeannine S MccuneAbstract:Abstract Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal Antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
Keith R Jerome - One of the best experts on this subject based on the ideXlab platform.
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a phase ii multicenter study of visilizumab humanized anti CD3 Antibody to treat steroid refractory acute graft versus host disease
Biology of Blood and Marrow Transplantation, 2005Co-Authors: Paul A Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, H Khoury, Pablo Parker, Keith R Jerome, Jeannine S MccuneAbstract:Abstract Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal Antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.