Monoclonal antibodie

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker. PATIENTS AND METHODS: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors...

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections (LRTI), particularly in neonates, infants and young children, with approximately 33 million infections worldwide each year. 1-2% of episodes lead to hospitalization. There are hardly any reliable epidemiological figures on hospitalization in adults, whose burden of disease from RSV is probably markedly underestimated. METHODS: This review is based on publications retrieved by a selective search in PubMed, with particular attention to recommendations for the prevention of RSV infection...

PURPOSE: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). METHODS: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes...

Peptide mapping with mass spectrometry (MS) is an important tool for protein characterization in the biopharmaceutical industry. Historically, peptide mapping monitors post-translational modifications (PTMs) of protein products and process intermediates during development. Multi-attribute monitoring (MAM) methods have been used previously in commercial release and stability testing panels to ensure control of selected critical quality attributes (CQAs). Our goal is to use MAM methods as part of an overall analytical testing strategy specifically focused on CQAs, while removing or replacing historical separation methods that do not effectively distinguish CQAs from non-CQAs due to co-elution...

PURPOSE OF THE REVIEW: Antiphospholipid syndrome (APS) is a rare systemic autoimmune disorder that can escalate into a 'thrombotic storm' called the catastrophic antiphospholipid syndrome (CAPS), frequently requiring ICU admission for multiple organ failure. This review aims to offer insight and recent evidence on critically-ill APS patients. RECENT FINDINGS: The CAPS classification criteria define this condition as the involvement of at least three organs/systems/tissues within less than a week, caused by small vessel thrombosis, in patients with elevated antiphospholipid antibodies levels...

PURPOSE: Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear. METHODS: We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission...

OBJECTIVE: There are currently 11 antibody-drug conjugates (ADC) that are FDA approved for use in oncologic disease states, with many more in the pipeline. The authors aim to review the pharmacokinetic profiles of the components of ADCs to engage pharmacist practitioners in practical considerations in the care of patients. This article provides an overview on the use of ADCs in the setting of organ dysfunction, drug-drug interactions, and management of on- and off-target adverse effects...

Chinese hamster ovary (CHO) cells are the commonly used mammalian host system to manufacture recombinant proteins including monoclonal antibodies. However unfavorable non-human glycoprofile displayed on CHO-produced monoclonal antibodies have negative impacts on product quality, pharmacokinetics, and therapeutic efficiency. Glycoengineering such as genetic elimination of genes involved in glycosylation pathway in CHO cells is a viable solution but constrained due to longer timeline and laborious workflow. Here, in this proof-of-concept (PoC) study, we present a novel approach coined CellEDIT to engineer CHO cells by intranuclear delivery of the CRISPR components to single cells using the FluidFM technology...

BACKGROUND: Retifanlimab is a humanized monoclonal antibody targeting programmed death protein-1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors. METHODS: Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2...

BACKGROUND: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important mediators of protection against the blood stages of the infection, but few studies have investigated this in the context of mAbs. We aimed to isolate mAbs agnostic to cognate antigens that target whole merozoites and simultaneously induce potent neutrophil activity measured by the level of reactive oxygen species (ROS) production using an antibody-dependent respiratory burst (ADRB) assay...

Hemophagocytic lymphohistiocytosis (HLH), whether primary or secondary, is a rare and fatal clinical syndrome of uncontrolled immune activation and inflammatory cascade. Immune checkpoint inhibitors (ICIs) induced HLH has no standard diagnostic and treatment guidelines. Early diagnosis and appropriate treatment according to different disease backgrounds are crucial. Herein, we first report 2 cases of patients with chronic active Epstein-Barr virus infection (CAEBV) who developed HLH after the use of sintilimab, a monoclonal antibody against programmed cell death protein 1 (PD-1), and the DEP (liposomal doxorubicin, etoposide, methylprednisolone) chemotherapy regimen in combination with ruxolitinib were used to successfully control the disease...

AIMS: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17A inhibitors, ixekizumab, and secukinumab, from the National Health Service (NHS) of Scotland perspective. METHODS: The axSpA treatment-pathway was modeled using a one-year decision tree followed by a lifetime Markov model...

The controlled expression of two or more proteins at a defined and stable ratio remains a substantial challenge, particularly in the bi- and multispecific antibody field. Achieving an optimal ratio of protein subunits can facilitate the assembly of multimeric proteins with high efficiency and minimize the production of by-products. In this study, we propose a solution based on alternative splicing, enabling the expression of a tunable and predefined ratio of two distinct polypeptide chains from the same pre-mRNA under the control of a single promoter...

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BACKGROUND: The impact of the constantly evolving severe acute respiratory syndrome coronavirus 2 on the effectiveness of early coronavirus disease 2019 (COVID-19) treatments is unclear. Here, we report characteristics and acute clinical outcomes of patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and predominance of Omicron subvariants (BA.1, BA.2, and BA.5) in England. METHODS: Retrospective cohort study using data from the Hospital Episode Statistics database from January 1-July 31, 2022...

Interferon (IFN) alpha/beta receptor 1 (IFNAR1) is indispensable for antiviral responses and the immune regulation. Dysregulation of the IFNAR1-mediaetd signaling pathways leads to deleterious autoimmune diseases such as systemic lupus erythematosus (SLE). QX006N, a humanized therapeutic monoclonal antibody, specifically targets human IFNAR1 and is in the clinical trial phase for treating SLE, but the molecular mechanism underlying the QX006N-mediated recognition of IFNAR1 remains unclear. Here, we report the high neutralization activities of QX006N against IFNAR1-mediated signal transduction...

In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC). Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis...

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse...

BACKGROUND: Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research. METHODS: The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement...

BACKGROUND: Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients...