ArticleThe AAPS journal2019
A Systems Pharmacology Model for Drug Delivery to Solid Tumors by Antibody-Drug Conjugates: Implications for Bystander Effects.
Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pooled it
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- Enfortumab vedotin induces immunogenic cell death and shows enhanced preclinical antitumor activity when combined with a PD-1 inhibitor.Cell reports. Medicine · 2026Article
- Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates' efficacy.Journal for immunotherapy of cancer · 2026Article
- Physicochemical and Metabolic Optimization of NAMPT Inhibitors Enables Effective Antibody-Drug Conjugates for Liquid and Solid Tumors.ACS bio & med chem Au · 2026Article
- In Vivo Auto-tuning of Antibody-Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies.Molecular cancer therapeutics · 2026Article
- Fc-Engineering Improves PET Imaging of Anti-Mesothelin VH-Fc across Multiple Tumor Mouse Models and Reveals Sex-Specific Renal Clearance.Bioconjugate chemistry · 2026Article
- Spatial PK-PD mismatch in tumor-targeting antibodies and ADCs: from lesion access to pharmacologic execution.Frontiers in oncology · 2026Review
- Determinants of sensitivity to HER2-targeted antibody drug conjugates in urothelial cancer.Nature communications · 2025Article
- SGNDV-001: disitamab vedotin with pembrolizumab in HER2-expressing locally advanced or metastatic urothelial carcinoma.Future oncology (London, England) · 2025Article
- Immunological mechanisms and antibody-drug conjugates targeting B7-H3 and B7-H4 in ovarian cancer.Frontiers in immunology · 2025Review
- Improving Intracellular Delivery of an Antibody-Drug Conjugate Targeting Carcinoembryonic Antigen Increases Efficacy at Clinically Relevant Doses In Vivo.Molecular cancer therapeutics · 2024Article
- Key considerations based on pharmacokinetic/pharmacodynamic in the design of antibody-drug conjugates.Frontiers in oncology · 2024Review
- SGN-B7H4V, an investigational vedotin ADC directed to the immune checkpoint ligand B7-H4, shows promising activity in preclinical models.Journal for immunotherapy of cancer · 2023Article
- Mechanistically Weighted Metric to Predict In Vivo Antibody-Receptor Occupancy: An Analytical Approach.The Journal of pharmacology and experimental therapeutics · 2023Article
- A Novel Dual-Payload ADC for the Treatment of HER2+ Breast and Colon Cancer.Pharmaceutics · 2023Article
- Antibody-Drug Conjugate Sacituzumab Govitecan Drives Efficient Tissue Penetration and Rapid Intracellular Drug Release.Molecular cancer therapeutics · 2023Article
- Pharmacokinetics and Pharmacodynamics of TAK-164 Antibody Drug Conjugate Coadministered with Unconjugated Antibody.The AAPS journal · 2022Article
- Integrated multiple analytes and semi-mechanistic population pharmacokinetic model of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Cellular-Resolution Imaging of Bystander Payload Tissue Penetration from Antibody-Drug Conjugates.Molecular cancer therapeutics · 2022Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Antibody-drug conjugates (ADCs) are cancer drugs composed of a humanized antibody linked to a cytotoxic payload, allowing preferential release of payload in cancer cells expressing the antibody-targeted antigen. Here, a systems pharmacology model is used to simulate ADC transport from blood to tumor tissue and ADC uptake by tumor cells. The model includes effects of spatial gradients in drug concentration in a three-dimensional network of tumor blood vessels with realistic geometry and accounts for diffusion of ADC in the tumor extracellular space, binding to antigen, internalization, intracellular processing, and payload efflux from cells. Cells that process an internalized ADC-antigen complex may release payload that can be taken up by other "bystander" cells. Such bystander effects are included in the model. The model is used to simulate conditions in previous experiments, showing good agreement with experimental results. Simulations are used to analyze the relationship of bystander effects to payload properties and single-dose administrations. The model indicates that exposure of payload to cells distant from vessels is sensitive to the free payload diffusivity in the extracellular space. When antigen expression is heterogeneous, the model indicates that the amount of payload accumulating in non-antigen-expressing cells increases linearly with dose but depends only weakly on the percentage of antigen-expressing cells. The model provides an integrated mechanistic framework for understanding the effects of spatial gradients on drug distribution using ADCs and for designing ADCs to achieve more effective payload distribution in solid tumors, thereby increasing the therapeutic index of the ADC.
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What OpenQuestion holds
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.