ArticleJournal of pharmacokinetics and pharmacodynamics2012
Bench to bedside translation of antibody drug conjugates using a multiscale mechanistic PK/PD model: a case study with brentuximab-vedotin.
Article in Journal of pharmacokinetics and pharmacodynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 153 citations in OpenAlex.
- Population Pharmacokinetics of Brentuximab Vedotin in Patients With CD30-Expressing Hematologic Malignancies.Journal of clinical pharmacology · 2017Trial
- Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026Review
- Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates' efficacy.Journal for immunotherapy of cancer · 2026Article
- From Unmet Medical Need to Drug Candidate: A Translational Therapeutic Development Roadmap Illustrated by Dual-Payload Antibody-Drug Conjugates.Biomolecules · 2026Review
- PK-PD Modeling Suggests Tumor Heterogeneity Limits Preclinical to Clinical Translation of Enzalutamide in Prostate Cancer.Pharmaceutical research · 2026Article
- Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy.PLoS computational biology · 2026Article
- Applications of Pharmacometrics in Antibody-Drug Conjugate Development.Pharmaceutics · 2026Review
- A mechanistic pharmacokinetic-pharmacodynamic model for degrader-antibody conjugates.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- A Proxy-guided Workflow for Virtual Population Development.The AAPS journal · 2025Article
- Mechanistic modeling suggests stroma-targeting antibody-drug conjugates as an alternative to cancer-targeting in cases of heterogeneous target exspression.PLoS computational biology · 2025Article
- Using mathematical modelling and AI to improve delivery and efficacy of therapies in cancer.Nature reviews. Cancer · 2025Review
- Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Towards a platform quantitative systems pharmacology (QSP) model for preclinical to clinical translation of antibody drug conjugates (ADCs).Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Formulation and Validation of an Extended Sigmoid Emax Model in Pharmacodynamics.Pharmaceutical research · 2024Article
- Clinical Pharmacology of the Antibody-Drug Conjugate Enfortumab Vedotin in Advanced Urothelial Carcinoma and Other Malignant Solid Tumors.Clinical pharmacokinetics · 2024Review
- Clinical validation of translational antibody PBPK model using tissue distribution data generated withJournal of pharmacokinetics and pharmacodynamics · 2023Article
- Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88.Clinical and translational science · 2023Article
- Pharmacokinetics and Pharmacodynamics of Antibody-Drug Conjugates Administered via Subcutaneous and Intratumoral Routes.Pharmaceutics · 2023Article
- Predictive Design and Analysis of Drug Transport by Multiscale Computational Models Under Uncertainty.Pharmaceutical research · 2023Review
- Counterion Tuning of Near-Infrared Organic Salts Dictates Phototoxicity to Inhibit Tumor Growth.ACS applied materials & interfaces · 2022Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To build a multiscale mechanism based pharmacokinetic-pharmacodynamic (PK/PD) model for antibody drug conjugates (ADCs), using brentuximab-vedotin as an example, for preclinical to clinical translation of ADC efficacy. Brentuximab-vedotin experimental data, collected from diverse publications, were employed in the following steps to build and validate the model: (1) characterization of ADC and payload PK at the cellular level, (2) characterization of payload PK in plasma and tumor tissue of xenograft mouse, (3) characterization of ADC PK in mouse plasma, (4) prediction of the tumor payload concentrations in xenograft mouse by integrating parameters obtained from steps 1-3 with the novel tumor disposition model for ADC, (5) characterization of preclinical brentuximab-vedotin tumor growth inhibition data using the novel PK/PD model, (6) characterization of ADC and payload PK in cancer patients, and (7) prediction of clinical responses of brentuximab-vedotin using the PK/PD model, by integrating PK parameters obtained from step 6, and translated mouse parameters from step 5; and comparing them with clinical trial results. The tumor disposition model was able to accurately predict xenograft tumor and plasma payload concentrations. PK/PD model predicted progression free survival rates and complete response rates for brentuximab-vedotin in patients were comparable to the observed clinical results. It is essential to understand and characterize the disposition of ADC and payload, at the cellular and physiological level, to predict the clinical outcome of ADC. A first of its kind mechanistic model has been developed for ADCs, which can integrate preclinical biomeasures and PK/PD data, to predict clinical response.
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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.