The current industry practice for antibody-drug conjugate (ADC) bioanalysis includes quantification of total antibody and antibody-conjugated drug. Here, we report a novel 2-in-1 approach for measuring total antibody and protease-cleavable conjugated drug Monomethyl Auristatin E (MMAE) concurrently. This allows for the determination of the DAR (Drug Antibody Ratio) for in vivo samples, with a 3-orders linear range based on total antibody concentration from 0.1 to 100 μg/mL. Our generic, concurrent method has been cross-validated with the previously established methods in an animal study. This novel approach is applicable to all human IgG1 ADCs with papain cleavable conjugated drug in preclinical studies.
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http://dx.doi.org/10.1016/j.ab.2017.08.024 | DOI Listing |
Blood
January 2025
Division of Immunology and Allergy, Children's Hospital of Philadelphia; Department of Pediatrics, Perelman School of Medicine; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Agricultural and Environmental Sciences, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brazil.
Chikungunya virus (CHIKV) is primarily associated with non-human-primates (NHPs) in Africa, which also infect humans. Since its introduction to Brazil in 2014, CHIKV has predominantly thrived in urban cycles, involving Aedes aegypti mosquitoes. Limited knowledge exists regarding CHIKV occurrence and implications in rural and sylvatic cycles where neotropical NHPs are potential hosts, from which we highlight Leontopithecus chrysomelas (Kuhl, 1820), the golden-headed lion tamarin (GHLT), an endangered species endemic to the Atlantic Forest (AF) in Southern Bahia State, Brazil.
View Article and Find Full Text PDFTransfus Med
January 2025
Hospital de Pediatría, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
Background: Worldwide, there has been a worrying increase in the prevalence of syphilis. Blood banks have a major role in monitoring the trend of these events, despite the bias due to the altruistic donation strategy.
Objectives: To determine the seroprevalence of syphilis and analyse its association with defined risk factors among blood donors at the regional blood center at Hospital Prof.
Clin Transl Gastroenterol
January 2025
Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.
Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.
Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24.
Cancer
February 2025
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.
Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.
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