A5005988952- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Caveolin-1 and cellular processes
- Proteoglycans and glycosaminoglycans research
- Bone health and treatments
- Glycosylation and Glycoproteins Research
- Biosimilars and Bioanalytical Methods
- Cancer Treatment and Pharmacology
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Advanced Biosensing Techniques and Applications
- Chronic Lymphocytic Leukemia Research
- Chemokine receptors and signaling
- Metabolism, Diabetes, and Cancer
- Platelet Disorders and Treatments
- Mass Spectrometry Techniques and Applications
- Antimicrobial Resistance in Staphylococcus
- Protein purification and stability
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Advanced Breast Cancer Therapies
- Biosensors and Analytical Detection
- Chronic Myeloid Leukemia Treatments
- Urological Disorders and Treatments
Bioanalytical Systems (United States)
2014-2024
Evelina London Children's Healthcare
2023-2024
Bioanalytica (Switzerland)
2024
Genentech
2012
Washington Hospital
2012
MedStar Washington Hospital Center
2012
Rapt Therapeutics (United States)
2011
Target (United States)
2011
University of California, Davis
2005-2008
University of California, Berkeley
2003-2005
Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate comprising trastuzumab and DM1, a microtubule polymerization inhibitor, covalently bound via stable thioether linker. To characterize the pharmacokinetics (PK) of T-DM1 in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, data from four studies (TDM3569g, TDM4258g, TDM4374g, TDM4688g) single-agent administered at 3.6 mg/kg every 3 weeks (q3w) were assessed aggregate. Multiple...
Antibody-drug conjugates (ADCs) are monoclonal antibodies with covalently bound cytotoxic drugs. They designed to target tumor antigens selectively and offer the hope of cancer treatment without debilitating side-effects conventional therapies. The concept ADCs is not new; however, development these therapeutics challenging only recently promising clinical data emerging. These challenges include ADC bioanalysis, such as quantifying in serum/plasma for PK studies strategies assessing...
Abstract Approved antibody-drug conjugates (ADCs) for HER2-positive breast cancer include trastuzumab emtansine and deruxtecan. To develop a differentiated HER2 ADC, we chose an antibody that does not compete with or pertuzumab binding, conjugated to reduced potency PBD (pyrrolobenzodiazepine) dimer payload. PBDs are potent cytotoxic agents alkylate cross-link DNA. In our study, the is modified alkylate, but This DHES0815A, demonstrates in vivo efficacy models of HER2-low cancers...
Antibody-drug conjugates (ADCs) are designed to combine the exquisite specificity of antibodies target tumor antigens with cytotoxic potency chemotherapeutic drugs. In addition general chemical stability linker, a thorough understanding relationship between ADC composition and biological disposition is necessary ensure that therapeutic window not compromised by altered pharmacokinetics (PK), tissue distribution, and/or potential organ toxicity. The six-transmembrane epithelial antigen...
Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs based on hypothesis that targeted delivery potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared non-targeted delivery, where poor can limit efficacious doses. Here, we present results from preclinical studies characterizing toxicity profile...
Abstract Purpose: Trastuzumab-emtansine (T-DM1) is an antibody–drug conjugate (ADC) comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable linker. Thrombocytopenia was dose-limiting toxicity in phase I study, and grade ≥3 thrombocytopenia occurred up 13% of patients receiving T-DM1 III studies. We investigated mechanism T-DM1–induced thrombocytopenia. Experimental Design: The effect on platelet function measured by aggregometry, flow cytometry detect markers activation....
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate in clinical development for the treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers. Herein, we describe a series studies to assess T-DM1 absorption, distribution, metabolism, and excretion (ADME) rats as well exposure catabolites. Following administration unlabeled radiolabeled female Sprague Dawley single dose, plasma, urine, bile feces were assessed mass balance, profiling identification In rats, major...
Staphylococcus aureus causes serious bacterial infections with high morbidity and mortality, necessitating the discovery of new antibiotics. DSTA4637S is a novel antibody-antibiotic conjugate designed to target intracellular S. that not adequately eliminated by current standard-of-care
DSTA4637A, a novel THIOMAB™ antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as potential therapy S. infections. Structurally, TAC composed of an anti-S. linked to potent antibiotic, dmDNA31. The goal the current study was characterize pharmacokinetics (PK) in mice, assess effect infection on its PK, and evaluate pharmacodynamics (PD) by measuring bacterial load various organs at different timepoints following treatment. Plasma...
The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place Orlando, FL, USA June 19–23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week allow an exhaustive thorough coverage all major issues bioanalysis biomarkers, immunogenicity, gene therapy, cell therapy vaccines....
A new method using a combination of electrospray ionization mass spectrometry (ESI-MS) and tandem (MSn) was developed for the identification quantitative analysis eight heparan sulfate (HS)- heparin-derived Δ-disaccharides obtained by enzymatic depolymerization. The compositional nonisomeric disaccharide constituents heparin/HS achieved from full-scan MS1 spectra an internal standard calculated response factor each disaccharide. Diagnostic product ions MSn isomeric disaccharides were used...
Heparin and heparan sulfate (HS) glycosaminoglycans have been identified as important players in many physiological well pathophysiological settings. A better understanding of the biosynthesis structure these molecules is critical for further elucidation their biological function. We demonstrated successful use negative electrospray ionization tandem mass spectrometry differentiation all twelve standard heparin-building blocks, including potentially N-unsubstituted disaccharides. Collision...
An important class of carbohydrates studied within the field glycobiology, heparin and heparan sulfate (HS) have been implicated in a diverse array biological functions. Changes their sulfation pattern domain organization associated with different pathological situations such as viral infectivity, tumor growth, metastasis. To obtain structural information about these biomolecules, modifications they may undergo during stages cell growth development, mass spectrometry-based method was...
CD22 represents a promising target for antibody-drug conjugate therapy in the context of B cell malignancies since it rapidly internalizes, importing specifically bound antibodies with it. To determine pharmacokinetic parameters anti-CD22-MCC-DM1 and MC-MMAF conjugates, various approaches to quantifying total conjugated antibody were investigated. Although assay formats gave similar results both mouse profile appeared significantly different depending on format. Since these differences...
Antibody-drug conjugates (ADCs) combine the characteristics of large-molecule biologics and small-molecule drugs are heterogeneous mixtures that can biotransform in vivo, resulting additional complexity. ADC bioanalytical strategies require novel analytical methods, as well existing large- methods. Because ADCs late-stage clinical development relatively new, regulatory guidelines standard industry best practices for developing PK assays still being established.A assay strategy was developed...
Glycosaminoglycans (GAGs) have recently been demonstrated to be required for the in vivo activity of several chemokines. Minimally, interaction is thought provide a mechanism retention at site secretion and formation chemokine gradients that directional cues receptor bearing cells, particularly presence shear forces. Thus, key issue will determine sequence structure GAGs bind specific Herein, we describe mass spectrometry assay was developed detect protein-oligosaccharide noncovalent...
Mass spectrometry, and specifically sequential stages of mass spectrometry (MSn), is an established tool for the analysis carbohydrates, proteins, more recently glycosaminoglycans. As this trend continues, development algorithms rapid automatic interpretation spectra to identify glycan structure also expected grow as active field research. The methodology described herein utilizes a combination enzymatic digestion, ESI-MS, MSn sequencing small heparin oligosaccharides. oligosaccharide (HOST)...
The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place San Antonio, TX, USA May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week allow an exhaustive thorough coverage all major issues bioanalysis biomarkers, immunogenicity, gene therapy, cell therapy...
Abstract Trastuzumab emtansine (T‐DM1) is an antibody‐drug conjugate in development for human epidermal growth factor receptor 2 (HER2)‐positive cancer. Drugs are generally tested their effects on QT interval, prolongation of which associated with the potentially fatal arrhythmia torsades de pointes. In addition, association between left ventricular dysfunction and other HER2‐directed agents has been documented. This multicenter, phase study, TDM4688g, assessed safety pharmacokinetic...
The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place Los Angeles/Universal City, California 3–7 April with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event – full immersion week bioanalysis, biomarkers immunogenicity. As usual, it specifically designed facilitate sharing, reviewing, discussing...
Aim: To evaluate the clinical immunogenicity of eight antibody–drug conjugates (ADCs), multi-domain biotherapeutics that could theoretically pose a greater risk than monoclonal antibodies (mAbs) because they contain non-natural structural motifs. Methodology & results: Immunogenicity strategies and assays for these ADCs included those commonly used conventional with additional characterization. A tiered approach was adopted testing Phase I II study samples screening, confirmatory domain...
DSTA4637S, a novel THIOMAB™ antibody-antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as potential therapy for complicated S. bloodstream infections. DSTA4637S composed of monoclonal THIOMABTM IgG1 recognizing linked to rifamycin-class antibiotic (dmDNA31) via protease-cleavable linker. The pharmacokinetics (PK) DSTA4637A (a liquid formulation DSTA4637S) and its unconjugated antibody MSTA3852A were characterized in rats monkeys. Systemic...