ArticleThe AAPS journal2020
Antibody Coadministration as a Strategy to Overcome Binding-Site Barrier for ADCs: a Quantitative Investigation.
Article in The AAPS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 65 citations in OpenAlex.
- ABL209 (NEOK002): Designing an EGFR × MUC1 Bispecific TOP1i ADC with Promising Antitumor Activity and Enhanced Therapeutic Window.Molecular cancer therapeutics · 2026Article
- Physicochemical and Metabolic Optimization of NAMPT Inhibitors Enables Effective Antibody-Drug Conjugates for Liquid and Solid Tumors.ACS bio & med chem Au · 2026Article
- Review
- Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review.International journal of molecular sciences · 2026Review
- Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy.PLoS computational biology · 2026Article
- Exposure-Response Relationships of Antibody Drug Conjugates in Solid Tumours.Clinical pharmacokinetics · 2026Review
- In Vivo Auto-tuning of Antibody-Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies.Molecular cancer therapeutics · 2026Article
- Sym024 Interacts with a Unique Epitope on the CD73 Homodimer, Favoring Effective Bivalent Binding to Improve Anti-PD-1 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Spatial PK-PD mismatch in tumor-targeting antibodies and ADCs: from lesion access to pharmacologic execution.Frontiers in oncology · 2026Review
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Application and Progress of Antibody-Drug Conjugates (ADCs) in the Treatment of Metastatic Triple-Negative Breast Cancer.Oncology and therapy · 2025Review
- Maximizing activity and selectivity of antibody-mediated effector functions using antibody mixtures.mAbs · 2025Article
- Leveraging the Tumor Microenvironment as a Target for Cancer Therapeutics: A Review of Emerging Opportunities.Pharmaceutics · 2025Review
- Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index.Cancers · 2025Review
- Opportunities and Challenges in Antibody-Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment.Cancers · 2025Review
- Diverse Roles of Antibodies in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Antibody Drug Conjugates (ADCs): Shaping the Future of Precision Oncology.Anti-cancer agents in medicinal chemistry · 2025Review
- Antibody-drug conjugate: a newly developed biological missile for tumor treatment.Frontiers in oncology · 2025Review
- HER2 expression in different cell lines at different inoculation sites assessed by [Pathology oncology research : POR · 2025Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
It has been proposed that the binding-site barrier (BSB) for antibody-drug conjugates (ADCs) can be overcome with the help of antibody coadministration. However, broad utility of this strategy remains in question. Consequently, here, we have conducted in vivo experiments and pharmacokinetics-pharmacodynamics (PK-PD) modeling and simulation (M&S) to further evaluate the antibody coadministration hypothesis in a quantitative manner. Two different Trastuzumab-based ADCs, T-DM1 (no bystander effect) and T-vc-MMAE (with a bystander effect), were evaluated in high-HER2 (N87) and low-HER2 (MDA-MB-453) expressing tumors, with or without the coadministration of 1, 3, or 8-fold higher Trastuzumab. The tumor growth inhibition (TGI) data was quantitatively characterized using a semi-mechanistic PK-PD model to determine the nature of drug interaction for each coadministration regimen, by estimating the interaction parameter ψ. It was found that the coadministration strategy improved ADC efficacy under certain conditions and had no impact on ADC efficacy in others. The benefit was more pronounced for N87 tumors with very high antigen expression levels where the effect on treatment was synergistic (a synergistic drug interaction, ψ = 2.86 [2.6-3.12]). The benefit was diminished in tumor with lower antigen expression (MDA-MB-453) and payload with bystander effect. Under these conditions, the coadministration regimens resulted in an additive or even less than additive benefit (ψ ≤ 1). As such, our results suggest that while antibody coadministration may be helpful for ADCs in certain circumstances, one should not broadly apply this strategy to all the scenarios without first identifying the costs and benefits of this approach.
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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.