ArticleJournal of pharmaceutical sciences2019
A "Dual" Cell-Level Systems PK-PD Model to Characterize the Bystander Effect of ADC.
Article in Journal of pharmaceutical sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Influence of antibody-drug conjugate cleavability, drug-to-antibody ratio, and free payload concentration on systemic toxicities: A systematic review and meta-analysis.Cancer metastasis reviews · 2024Pooled it
- Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates' efficacy.Journal for immunotherapy of cancer · 2026Article
- Cellular Heterogeneity in Drug Uptake Amplifies Pharmacodynamic Variability: A Stochastic PK-PD Analysis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy.PLoS computational biology · 2026Article
- Review
- Past, present and future of drug conjugates for cancer therapy.Nature cancer · 2025Review
- Mechanistic modeling suggests stroma-targeting antibody-drug conjugates as an alternative to cancer-targeting in cases of heterogeneous target exspression.PLoS computational biology · 2025Article
- Antibody-drug conjugate: a newly developed biological missile for tumor treatment.Frontiers in oncology · 2025Review
- Key considerations based on pharmacokinetic/pharmacodynamic in the design of antibody-drug conjugates.Frontiers in oncology · 2024Review
- Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates.iScience · 2023Review
- Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?Acta pharmaceutica Sinica. B · 2023Review
- Development of and insights from systems pharmacology models of antibody-drug conjugates.CPT: pharmacometrics & systems pharmacology · 2022Review
- A comprehensive review on antibody-drug conjugates (ADCs) in the treatment landscape of non-small cell lung cancer (NSCLC).Cancer treatment reviews · 2022Review
- Antibody drug conjugate: the "biological missile" for targeted cancer therapy.Signal transduction and targeted therapy · 2022Review
- Bivalent EGFR-Targeting DARPin-MMAE Conjugates.International journal of molecular sciences · 2022Article
- Evolution of the Systems Pharmacokinetics-Pharmacodynamics Model for Antibody-Drug Conjugates to Characterize Tumor Heterogeneity andThe Journal of pharmacology and experimental therapeutics · 2020Article
- An Agent-Based Systems Pharmacology Model of the Antibody-Drug Conjugate Kadcyla to Predict Efficacy of Different Dosing Regimens.The AAPS journal · 2020Article
- A Cell-Level Systems PK-PD Model to Characterize In Vivo Efficacy of ADCs.Pharmaceutics · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Here, we have developed a cell-level systems PK-PD model to characterize the bystander effect of antibody-drug conjugates (ADCs). Cytotoxicity data generated following incubation of Trastuzumab-vc-MMAE in cocultures of high HER2-expressing N87 and low HER2-expressing GFP-MCF7 cells were used to build the model. Single-cell PK model for ADC was used to characterize the PK of trastuzumab-vc-MMAE and released MMAE in N87 and GFP-MCF7 cells. The 2 cell-level PK models were mechanistically integrated to mimic the coculture condition. MMAE-induced intracellular occupancy of tubulin was used to drive the efficacy of ADC, and improvement in the tubulin occupancy of GFP-MCF7 cells in the presence of N87 cells was used to drive the bystander effect of trastuzumab-vc-MMAE. The "dual" cell-level PK-PD model was able to capture the observed data reasonably well. It was found that similar and high occupancy of tubulin by MMAE was required to achieve the cytotoxic effect in each cell line. In addition, estimated model parameters suggested that ∼60% improvement in the tubulin occupancy was required to attain half of the maximum bystander killing effect by the ADC. The presented model provides foundation for in vivo systems PK-PD model to characterize and predict the bystander effect of ADCs.
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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.