ArticlemAbs
Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMAB™ antibody antibiotic conjugate against Staphylococcus aureus in mice.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- A Phase 1, Randomized, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S, an Anti-Antimicrobial agents and chemotherapy · 2019Trial
- Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial.Intensive care medicine · 2018Trial
- Immunotherapeutic modalities for combating multidrug-resistant bacteria: therapeutic promises of antibodies and next-generation vaccines.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Perspective Approaches to "Trojan Horse" Strategy Development for Combating Bacterial Pathogens.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Antibody-Antibiotic Conjugates: Mechanisms, Clinical Progress, and Next-Generation Strategies Against Multidrug-Resistant Bacterial Infections.MicrobiologyOpen · 2026Review
- Mechanistic Characterization of the Potency of THIOMAB Antibody-Drug Conjugates TargetingBioconjugate chemistry · 2025Article
- Flycodes enable simultaneous preclinical analysis for dozens of antibodies in single cassette-dosed mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The endothelium at the interface between tissues andClinical microbiology reviews · 2025Review
- Review
- Advances in the targeted theragnostics of osteomyelitis caused by Staphylococcus aureus.Archives of microbiology · 2024Review
- Alternative therapeutic strategies to treat antibiotic-resistant pathogens.Nature reviews. Microbiology · 2024Review
- Antibody-Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections.Journal of clinical laboratory analysis · 2024Review
- Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era.Life (Basel, Switzerland) · 2024Review
- Treatment of MRSA Infection: Where are We?Current medicinal chemistry · 2024Review
- Introduction of Carbonyl Groups into Antibodies.Molecules (Basel, Switzerland) · 2023Review
- Development of Apoptotic-Cell-Inspired Antibody-Drug Conjugate for Effective Immune Modulation.International journal of molecular sciences · 2023Article
- Strategy to combat biofilms: a focus on biofilm dispersal enzymes.NPJ biofilms and microbiomes · 2023Review
- Review
- Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DSTA4637A, a novel THIOMAB™ antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as a potential therapy against S. aureus infections. Structurally, TAC is composed of an anti-S. aureus antibody linked to a potent antibiotic, dmDNA31. The goal of the current study was to characterize the pharmacokinetics (PK) of TAC in mice, assess the effect of S. aureus infection on its PK, and evaluate its pharmacodynamics (PD) by measuring the bacterial load in various organs at different timepoints following TAC treatment. Plasma concentrations of 3 analytes, total antibody (TAb), antibody-conjugated dmDNA31 (ac-dmDNA31), and unconjugated dmDNA31, were measured in these studies. In non-infected mice (target antigen absent), following intravenous (IV) administration of a single dose of TAC, systemic concentration-time profiles of both TAb and ac-dmDNA31 were bi-exponential and characterized by a short distribution phase and a long elimination phase as expected for a monoclonal antibody-based therapeutic. Systemic exposures of both TAb and ac-dmDNA31 were dose proportional over the dose range tested (5 to 50 mg/kg). In a mouse model of systemic S. aureus infection (target antigen present), a single IV dose of TAC demonstrated PK behavior similar to that in the non-infected mice, and substantially reduced bacterial load in the heart, kidney, and bones on 7 and 14 d post dosing. These findings have increased our understanding of the PK and PK/PD of this novel molecule, and have shown that at efficacious dose levels the presence of S. aureus infection had minimal effect on TAC PK.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.