ArticlePloS one2015
A mechanistic tumor penetration model to guide antibody drug conjugate design.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed.
- Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026Review
- Site-specific trastuzumab Fab-DM1 via butelase-1 with ABD fusion for potent HER2-positive tumor control.Medical oncology (Northwood, London, England) · 2026Article
- The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer.NPJ precision oncology · 2025Review
- Exploring Experimental and In Silico Approaches for Antibody-Drug Conjugates in Oncology Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Advancements in molecular imaging probes for precision diagnosis and treatment of prostate cancer.Journal of Zhejiang University. Science. B · 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
- Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition.Nature reviews. Drug discovery · 2024Review
- Single-Domain Antibodies as Antibody-Drug Conjugates: From Promise to Practice-A Systematic Review.Cancers · 2024Review
- Improving Intracellular Delivery of an Antibody-Drug Conjugate Targeting Carcinoembryonic Antigen Increases Efficacy at Clinically Relevant Doses In Vivo.Molecular cancer therapeutics · 2024Article
- Targeted Nanofitin-drug Conjugates Achieve Efficient Tumor Delivery and Therapeutic Effect in an EGFRpos Mouse Xenograft Model.Molecular cancer therapeutics · 2023Article
- Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies?Marine drugs · 2023Review
- Passive Membrane Permeability of Sizable Acyclic β-Hairpin Peptides.ACS medicinal chemistry letters · 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
- A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Development of and insights from systems pharmacology models of antibody-drug conjugates.CPT: pharmacometrics & systems pharmacology · 2022Review
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Simulating the Selection of Resistant Cells with Bystander Killing and Antibody Coadministration in Heterogeneous Human Epidermal Growth Factor Receptor 2-Positive Tumors.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Mechanistic Modeling of Intra-Tumor Spatial Distribution of Antibody-Drug Conjugates: Insights into Dosing Strategies in Oncology.Clinical and translational science · 2021Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody drug conjugates (ADCs) represent novel anti-cancer modalities engineered to specifically target and kill tumor cells expressing corresponding antigens. Due to their large size and their complex kinetics, these therapeutic agents often face heterogeneous distributions in tumors, leading to large untargeted regions that escape therapy. We present a modeling framework which includes the systemic distribution, vascular permeability, interstitial transport, as well as binding and payload release kinetics of ADC-therapeutic agents in mouse xenografts. We focused, in particular, on receptor dynamics such as endocytic trafficking mechanisms within cancer cells, to simulate their impact on tumor mass shrinkage upon ADC administration. Our model identified undesirable tumor properties that can impair ADC tissue homogeneity, further compromising ADC success, and explored ADC design optimization scenarios to counteract upon such unfavorable intrinsic tumor tissue attributes. We further demonstrated the profound impact of cytotoxic payload release mechanisms and the role of bystander killing effects on tumor shrinkage. This model platform affords a customizable simulation environment which can aid with experimental data interpretation and the design of ADC therapeutic treatments.
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