Effectiveness of a Second Course of OKT3 Monoclonal Anti-T Cell Antibody for Treatment of Renal Allograft Rejection

Norman, Douglas J.; Shield, Charles F.; Henell, K.; Kimball, Jess; Barry, John M.; Bennett, William M.; Leone, Michael

doi:10.1016/s0022-5347(17)41369-3

Cited by 10 publications

(12 citation statements)

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“…Several studies have shown that the majority of patients (>70%) with low antibody titres measured by ELISA experienced rever sal of rejection after muromonab CD3 re-treatment. [245][246][247] Howe ver, the ELISA method does not distingui sh between anti-idiotype and anti-i sotyp e antibodies, is difficult to standardise, and is cumbersome to perform on small numbers of samples.l21 9.222] Other assays, such as the immunofluorescence inhibition test, [244] flow cytometry, [248] and a new membrane-based Irnmunoassay.t-t" aim to improve the selective detection of anti-idiotypic antibodies and maintain ease of performance. The membranebased immunoassay was compared with the ELISA: the result s for the 2 methods correlated well, [249] although the only strong advantage of the membrane-based method over the ELISA was the rapid turnaround time of 15 minute s for the former.…”

Section: Anti-muromonab Cd3 Antibody Monitoringmentioning

confidence: 99%

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

Tsunoda

Aweeka

1996

Clinical Pharmacokinetics

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Most experience of the therapeutic drug monitoring of immunosuppressive agents has been acquired in the field of solid organ transplantation; however, agents such as cyclosporin (cyclosporin A) are being increasingly utilised for the management of autoimmune diseases. Cyclosporin is the most widely studied immunosuppressant, but in spite of this many controversies still exist as to the optimum strategy for monitoring this drug. Owing to its widely variable pharmacokinetics and metabolism, and the absence of a simple method to measure therapeutic effectiveness, many factors should be considered. In most circumstances, measuring whole blood through concentrations of cyclosporin with a specific assay methodology is warranted. In addition, knowledge of other factors that may alter the pharmacokinetics (such as liver function, concomitant food or medications, gastrointestinal status, and time since transplantation) should be taken into account so that therapy can be appropriately adjusted. Other methods of monitoring have been investigated, such as AUC (area under the concentration-time curve) monitoring and immunological monitoring. However, further refinement of these techniques and greater experience with their efficacy must be accumulated before their role in the monitoring of cyclosporin can be defined. Tacrolimus, like cyclosporin, shares many of the difficulties in monitoring for efficacy and toxicity due largely to the variable pharmacokinetics; similarly to cyclosporin, whole blood through concentration monitoring should be utilised in combination with knowledge of the factors that may affect the pharmacokinetics. Muromonab CD3 (OKT3) is a monoclonal antibody used for the treatment and prophylaxis of acute allograft rejection. Several immunological monitoring techniques have been investigated for this agent. Monitoring CD3+ levels can assist clinicians in determining therapeutic efficacy, while measuring antimuromonab CD3 antibody titres can help determine if xenosensitisation has occurred, causing therapeutic ineffectiveness. The clinical monitoring of azathioprine, one of the first immunosuppressive agents used in transplantation, has historically been limited to monitoring complete blood counts for bone marrow suppression. However, newer techniques measuring intracellular DNA nucleotides appear to be promising. The new immunosuppressants on the horizon include mycophenolate mofetil and rapamycin. The clinical experience with therapeutic drug monitoring of these 2 compounds is scant in the literature; however, both agents have demonstrated efficacy in preventing or treating allograft rejection while maintaining a relatively well tolerated toxicity profile in recent clinical trials. Routine monitoring does not appear to be warranted for immunosuppressive therapy in autoimmune diseases.

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Section: Anti-muromonab Cd3 Antibody Monitoringmentioning

confidence: 99%

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

Tsunoda

Aweeka

1996

Clinical Pharmacokinetics

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“…OKT3, a murine anti-CD3 mAb currently approved for treatment and prevention of graft-versus-host disease (GVHD) is an effective immunosuppressant. However, it elicits severe CRS, which poses a serious limitation to its clinical applications [1][2][3][4][5]. To address this problem, a humanized version of OKT3, visilizumab/HuM291 (Nuvion w ) [6], is engineered with a reduced affinity for FcgR.…”

Section: Antibodies To Co-receptor Moleculesmentioning

confidence: 99%

T cell targeted immunotherapy for autoimmune disease

Lee

Sinha

2005

Autoimmunity

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Much emphasis has been placed on the so-called "biologics" in the treatment of immune disorders within the last few years. Here we discuss the expanding horizon of potential strategies for immunotherapies targeting T lymphocytes as key effectors and regulators of autoimmunity. We review emerging reagents in a variety of animal models and human disorders that may offer new therapeutic options in current or modified iterations.

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“…The first monoclonal antibody approved by the Food and Drug Administration (FDA) for use in humans was an immunosuppressive murine anti-CD3 epsilon subunit monoclonal antibody named Orthoclone OKT3 Ò (muromonab-CD3), indicated for the treatment or prevention of organ transplant rejection in patients receiving a donor heart, kidney, or liver (Chatenoud and Bluestone 2007). It was recognized early on that individuals receiving OKT3 developed immune responses against the murine variable and constant regions that could neutralize the immunosuppressive properties of the therapeutic (Legendre et al 1992;Norman et al 1988;Woodle et al 1991). Additionally, many patients exhibited a first dose reaction within hours of OKT3 administration, characterized by increased levels of cytokines (Chatenoud et al 1990), presumably due to interactions between the murine Fc region and human FccRs (Alegre et al 1994;Xu et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Application of Antibody Engineering in the Development of Next Generation Antibody-Based Therapeutics

Brezski¹,

Almagro²

2012

Development of Antibody-Based Therapeutics

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The evolution of therapeutic antibodies has encompassed multiple engineering efforts in the hope of improving the efficacy, safety, and duration of effects of antibody-based drugs. Advances in protein engineering technologies afforded investigators the ability to overcome problems associated with introducing foreign antibodies into humans. These efforts included antibody chimerization, humanization, and the more recent development of human antibodies, all of which reduced anti-drug immune responses. Additional efforts have engineered antibody variable regions that encode multiple specificities into a single molecular entity. Apart from optimizing antigen-binding capabilities and reducing immunogenicity, many advances have been made that modulate an antibody's ability to interact with cells and serum components of the immune system. Manipulation of antibody glycosylation or the amino acid sequence has had a significant impact on recruitment of the Fc-dependent effector functions. This chapter presents an overview of V region and Fc modifications and focuses on advances in engineering to tailor an antibody's function relative to the intended therapeutic need.

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Effectiveness of a Second Course of OKT3 Monoclonal Anti-T Cell Antibody for Treatment of Renal Allograft Rejection

Cited by 10 publications

References 0 publications

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

T cell targeted immunotherapy for autoimmune disease

Application of Antibody Engineering in the Development of Next Generation Antibody-Based Therapeutics

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