Orthoclone OKT3 (muromonab-CD3) / J&J - LARVOL DELTA

Development of a novel CD3ε-specific human antibody for selective modulation of T cell activation. (PubMed, Int J Biol Macromol) - "K108.5 also inhibited T cell activation induced by dendritic cells or muromonab-CD3 engagement. These findings suggest that K108.5 may be effective in modulating T cell activity under conditions of T cell dysregulation."

Journal • Immune Modulation • Immunology

Incidence and risk factors for skin cancer after heart transplantation: a systematic review and meta-analysis. (PubMed, Arch Dermatol Res) - "Risk factors significantly associated with skin cancer included age (RR: 1.08, 95% CI: 1.04-1.11), male (RR: 1.53, 95% CI:1.11-2.12), white race (RR: 10.23, 95% CI: 7.32-14.30), smoking history (RR:1.26, 95% CI:1.05-1.51), prolonged sunlight exposure (≥ 2500 h) (RR:3.66, 95% CI: 2.11-6.36), pre-transplant cancer (RR: 1.61, 95% CI: 1.43-1.82), muromonab-CD3 (OKT3) (RR: 2.61, 95% CI: 2.11-3.24)...YYS, FYL, and HPY, were responsible for the acquisition, analysis and interpretation of the data. All of the authors drafted the article or revised it critically for important intellectual content and provided final approval of the version to be submitted."

Clinical • Journal • Retrospective data • Review • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Squamous Cell Carcinoma • Transplantation

MORE THAN MEETS THE EYE: LIFE-THREATENING CYTOKINE RELEASE SYNDROME FOLLOWING METASTATIC UVEAL MELANOMA TREATMENT WITH TEBENTAFUSP (CHEST 2024) - "CRS was first documented in the 1990s with the use of anti-T-cell antibody muromonab-CD3 for immunosuppression following solid organ transplantation. While CRS is a notable adverse effect of tebentafusp-tebn, its presentation is highly variable and can rapidly progress to a dysregulated systemic inflammatory response requiring timely identification and multidisciplinary management of multiorgan system failure."

Cytokine release syndrome • Metastases • Acute Kidney Injury • Eye Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Hypotension • Immunology • Melanoma • Metabolic Disorders • Musculoskeletal Pain • Ocular Inflammation • Oncology • Pain • Pulmonary Disease • Renal Disease • Respiratory Diseases • Solid Organ Transplantation • Solid Tumor • Systemic Inflammatory Response Syndrome • Uveal Melanoma • HLA-A • IFNG • IL10 • IL6 • TNFA

Teplizumab in Type 1 Diabetes Mellitus: An Updated Review. (PubMed, touchREV Endocrinol) - "Muromonab-CD3, which also happened to be a murine CD3 antibody, was the first monoclonal antibody approved for clinical use and was primarily indicated for graft rejection. The mechanism seems to be enhancing regulatory T-cell activity and promoting immune tolerance. This article reviews the mechanism of action and the clinical trials of teplizumab in individuals with T1DM or at risk of developing the disease."

Journal • Review • Diabetes • Immunology • Metabolic Disorders • Transplant Rejection • Type 1 Diabetes Mellitus

Identification of potential therapeutic drugs targeting core genes for systemic lupus erythematosus (SLE) and coexisting COVID-19: Insights from bioinformatic analyses. (PubMed, Immun Inflamm Dis) - "Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Respiratory Diseases • Systemic Lupus Erythematosus • CD3E • CD40LG • CD5 • CD7 • GZMK • IL7R • KLRB1

Application of Computational Techniques in Antibody Fc-Fused Molecule Design for Therapeutics. (PubMed, Mol Biotechnol) - "Since the advent of hybridoma technology in the year 1975, it took a decade to witness the first approved monoclonal antibody Orthoclone OKT39 (muromonab-CD3) in the year 1986...In this article, we discuss the recent works in the Fc-fused molecule design that involves computational techniques. We also summarize the usefulness of in silico techniques to aid Fc-fused molecule design and analysis for the therapeutics application."

Journal • Review • Infectious Disease

Monoclonal antibodies and antibody-drug conjugates as emerging therapeutics for breast cancer treatment. (PubMed, Curr Drug Deliv) - "There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available...This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multispecific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Genetic code expansion in E. coli enables production of a functional 'ready-to-click' T cell receptor-specific scFv. (PubMed, N Biotechnol) - "Here, we optimized the soluble periplasmic expression of the scFv OKT3 comprising the variable V and V domains of the mouse anti-human CD3 antibody muromonab-CD3 (trade name Orthoclone OKT3) in E. coli...The scFv OKT3 wild type and the AzK variants bound T cells at nanomolar concentrations. In this study, a 'ready-to-click' scFv OKT3 was successfully developed for future applications, e.g. as controlled anti-T cell antibody-drug conjugate or bispecific T cell engager and for imaging immune T cell migration in cancers."

IO biomarker • Journal • Oncology

MASSIVE FLASH PULMONARY EDEMA FOLLOWING ANTIBODY-MEDIATED REJECTION THERAPY POST-LUNG TRANSPLANT (SCCM 2023) - "He was started on our institution-specific AMR protocol: systemic steroids, rituximab, a 5–7-day course of plasmapheresis, mepolizumab, and daratumumab... There are no reports of flash pulmonary edema after daratumumab administration, however it has been described with other monoclonal antibodies, including muromonab-CD3 (OKT3) [1]...We suspect a massive response of the infused monoclonal antibody with the pulmonary DSAs, resulting in localized cell death and lysis, cytokine release, pulmonary vascular inflammation, and uncontrollable pulmonary edema. We hope to gain further insight with immunohistological data on autopsy."

Acute Kidney Injury • Antibody-mediated Rejection • Cardiovascular • CNS Disorders • Hepatology • Hypertension • Immunology • Inflammation • Nephrology • Respiratory Diseases • Transplantation

Development of therapeutic antibodies for the treatment of diseases. (PubMed, Mol Biomed) - "Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 antibody drugs have been approved or are under regulatory review worldwide...Additionally, therapeutic antibodies can be combined with technologies used in other fields to create new cross-fields, such as chimeric antigen receptor T cells (CAR-T), CAR-natural killer cells (CAR-NK), and other cell therapy. This review summarizes the latest approved or in regulatory review therapeutic antibodies that have been approved or that are under regulatory review worldwide, as well as clinical research on these approaches and their development, and outlines antibody discovery strategies that have emerged during the development of therapeutic antibodies, such as hybridoma technology, phage display, preparation of fully human antibody from transgenic mice, single B-cell antibody technology, and artificial intelligence-assisted antibody discovery."

Journal • Review • Immunology • Metabolic Disorders • Oncology

Risk-Based Control Strategies of Recombinant Monoclonal Antibody Charge Variants. (PubMed, Antibodies (Basel)) - "Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care...Otherwise, new peaks or varied levels of acidic and basic species must be justified based on scientific knowledge and clinical experience for a specific molecule. Here, we summarize the current understanding of mAb charge variants and outline risk-based control strategies to support process development and ultimately commercialization."

Journal • Review • Immunology • Transplant Rejection • Transplantation

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections. (PubMed, Biomedicines) - "Since the first therapeutic mAb, muromonab-CD3, was approved by the U.S. Food and Drug Administration (FDA) in 1986, the list of approved mAbs and their clinical indications and applications have been proliferating...Gene delivery technologies, such as non-viral synthetic plasmid DNA and messenger RNA vectors (DMabs or mRNA-encoded mAbs), built to express tailored mAb genes, might help overcome some of the challenges of mAb therapy, including production restrictions, cold-chain storage, transportation requirements, and expensive manufacturing and distribution processes. This paper reviews some of the recent developments in mAb discovery against viral infections and illustrates how mAbs can help to combat viral diseases and outbreaks."

Journal • Review • Infectious Disease

Survivin; a novel therapeutic target that correlates with survival of autoreactive T lymphocytes obtained from patients with Ankylosing Spondylitis. (PubMed, Gene) - "Then, the isolated T cells were co-cultured with interleukin (IL)-2 and muromonab-CD3 (OKT-3) for active-induced cell death (AICD) induction, Survivin siRNA for inhibition of Survivin expression, and their combination to assess the implication of Survivin expression in autoreactive T lymphocytes' resistance to apoptosis by determining the rate of apoptosis by Flowcytometry assay...It was also revealed that T cells obtained from AS patients were more resistant to apoptosis induction than those obtained from healthy people. In summary, the results obtained from this study showed that dysregulation of Survivin and Survivin-targeting miRNAs in T lymphocytes obtained from AS patients contribute to their resistance to apoptosis, suggesting the future development of targeted therapies for AS."

Journal • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • BIRC5 • CASP9

Development of a flow cytometry-based potency assay for prediction of cytokine storms induced by biosimilar monoclonal antibodies. (PubMed, J Immunol Methods) - "We found that stimulation using solid phase (SP) dry coating with two different CD28 antibodies and muromonab-CD3 increased the percentage of IFN-ɣ + CD4+ and CD8+ T cells as well as of CD3-CD56+ NK cells compared to stimulation with antibodies in aqueous phase (AP)...Our findings demonstrated that flow cytometry analyses for assessing relevant T cell and NK cell markers may be used as a supplement to multiplex cytokine analysis in CRAs. The approach may be a valuable addition that enables a more precise description of the mechanisms leading to CRS."

Cytokine storm • Journal • Inflammation • CD4 • CD69 • CD8 • CSF2 • IL2RA • NCAM1 • TNFA

Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea? (PubMed, Front Med (Lausanne)) - "The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence...In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide."

Journal • Review • Immunology • Infectious Disease • Malaria • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Transplant Rejection • Transplantation

[VIRTUAL] COMPLEX CASE OF GIANT CELL MYOCARDITIS WITH PRIMARY GRAFT FAILURE POST TRANSPLANT (CHEST 2021) - "Patient was also found to have sustained VT for which she was treated with amiodarone and transferred to our facility for advanced heart failure evaluation.On arrival patient was taken for a RHC that showed CVP of 19, PA mean 35, wedge 28 cardiac index of 1.3 and mixed venous saturation of 30...She was started on IV methylprednisolone, IVIG, low-dose tacrolimus and mycophenolate.Patient continued to be in polymorphic VT and no signs of myocardial recovery was noted...Treatment with corticosteroids, tacrolimus, cyclosporine, muromonab CD3 have shown better outcomes (12.6 months vs. 3.0 months for no immunosuppression) (3).Definitive treatment of GCA remains cardiac transplant... GCA should be considered early on in patients presenting with new onset acute or acute on chronic CHF with higher clinical suspicion in those who require significant hemodynamic support or have ventricular tachyarrhythmias. Endomyocardial biopsy should be done earlier if suspicion of GCA exists."

Clinical • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Inflammation • Pulmonary Disease • Transplantation • Ventricular Tachycardia

Peripheral T-cell lymphoma immunophenotype in a patient with a history of Muromonab-CD3 therapy: A case report and a diagnostic dilemma. (PubMed, Cytometry B Clin Cytom) - No abstract available

Clinical • Journal • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Development of the first reference antibody panel for qualification and validation of cytokine release assay platforms - Report of an international collaborative study. (PubMed, Cytokine X) - "To address this issue, the National Institute for Biological Standards and Control (NIBSC) developed a reference panel of lyophilised mAbs known to induce CRS in the clinic: human anti-CD52, mouse anti-CD3 and human superagonistic (SA) anti-CD28 mAb manufactured according to the respective published sequences of Campath-1H® (alemtuzumab, IgG1) , Orthoclone OKT-3® (muromonab, IgG2a) and TGN1412 (theralizumab, IgG4), as well as three isotype matched negative controls (human IgG1, mouse IgG2a and human IgG4, respectively). The relative capacity of these control mAbs to stimulate the release of IFN-γ, IL-2, TNF-α and IL-6 in vitro was evaluated in eleven laboratories in an international collaborative study mediated through the HESI Immuno-safety Technical Committee Cytokine Release Assay Working Group. Therefore, the positive and negative mAbs are suitable as a reference panel for the qualification and validation of CRAs, comparison of different CRA platforms..."

Journal • Immune Modulation • Immunology • Inflammation • Systemic Inflammatory Response Syndrome • CD52 • IFNG • IL2 • IL6 • TNFA

Variable Benefits of Antibody Induction by Kidney Allograft Type. (PubMed, J Surg Res) - "While seemingly beneficial for recipients of all kidneys, induction has more robust associations with lower graft failure and acute rejection probability for recipients of ARF kidneys. Given the lack of observed benefit for ECD recipients, induction policies should be carefully considered in these patients."

Journal • Acute Kidney Injury • Cardiovascular • CNS Disorders • Graft versus Host Disease • Immunology • Transplantation

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Immune Therapy. (PubMed) - Pediatr Crit Care Med - "Immunomodulation has a crucial role in the treatment of certain pediatric cardiac diseases. Immunomodulatory treatments that have been used to treat myocarditis include corticosteroids, IV immunoglobulin, cyclosporine, and azathioprine. Contemporary outcomes of pediatric transplant recipients have improved over the past few decades, partly related to improvements in immunomodulatory therapy to prevent rejection of the donor heart. Immunosuppression therapy is commonly divided into induction, maintenance, and acute rejection therapy. Common induction medications include antithymocyte globulin, muromonab-CD3, and basiliximab. Maintenance therapy includes chronic medications that are used daily to prevent rejection episodes. Examples of maintenance medications are corticosteroids, cyclosporine, tacrolimus, sirolimus, everolimus, azathioprine, and mycophenolate mofetil. Rejection of the donor heart is diagnosed either by clinically or by biopsy and is t

Journal • Biosimilar • Heart Failure • Immunology

Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies (clinicaltrials.gov) - P2; N=73; Completed; Sponsor: St. Jude Children's Research Hospital; Trial completion date: Dec 2018 ➔ Feb 2020

Clinical • Trial completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Transplantation

Drug-Induced Progressive Multifocal Leukoencephalopathy: A Comprehensive Analysis of the WHO Adverse Drug Reaction Database. (PubMed) - "We report a possible association between several drugs and PML that has not been previously described. In addition, we have confirmed previously reported signals in a number of drugs. We highlight the need for follow-up by regulatory agencies."

Journal • Biosimilar

Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies (clinicaltrials.gov) - P2; N=73; Completed; Sponsor: St. Jude Children's Research Hospital; Active, not recruiting ➔ Completed

Clinical • Trial completion

Monoclonal Antibodies: A Review. (PubMed, Curr Clin Pharmacol) - "...Muromonab CD3 a murine MAb was the first FDA approved therapeutic MAb for the prevention of kidney transplant rejection. Since its approval in 1986, there has been a decline in further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of lowgrade B cell lymphoma in 1997...Mab are approved for the treatment of orphan diseases or indications such as paroxysmal nocturnal hemoglobinuria as well as cancers and multiple sclerosis where hundreds of patients are treated and even diseases such as breast cancer, asthma and rheumatoid arthritis where millions are being treated. This review focuses briefly on types, molecular targets, mechanism of actions and therapeutic indications of FDA approved MAb products that are currently on the market."

Journal

Mimicking virotherapy-elicited human cytokine storm using humanized mice (AACR 2019) - "CRS has been seen with several therapeutic biologics such as monoclonal antibodies (mAbs), including, rituximab, muromonab-CD3 and TGN1412. Administration of a specific replication competent viral vector resulted in acute toxicity, evidenced by sudden and significant body weight loss and mortality in such humanized mice, reflective of typical clinical symptoms of CRS, therefore suggesting a potential CRS model of human dysfunctional immune system. In the current study, we are performing comprehensive investigation of this potential CRS system by testing a variety of parameters, including dose titration, multiple routes of administrations (intraperitoneal, intravenous as a representation of slow and rapid infusion respectively, and intratumoral), safety assessments, including survival and clinical signs (appearance, behavior and body weight), as well as lymphocyte activation markers, laboratory tests of plasma cytokines, and viremia levels, etc. We believe that immune..."

Preclinical