ArticleThe AAPS journal2019
A Translational Quantitative Systems Pharmacology Model for CD3 Bispecific Molecules: Application to Quantify T Cell-Mediated Tumor Cell Killing by P-Cadherin LP DART
Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Global development of bispecific antibodies in oncology: a bibliometric analysis of geographic disparities, collaborative models, and emerging translational strategies.Frontiers in immunology · 2026Pooled it
- Clinical Validation of a QSP Model for ISB 2001, a Trispecific T Cell Engager to Support Optimal FIH Study Design in RRMM Patients.Clinical pharmacology and therapeutics · 2026Trial
- Dose Selection for DuoBody®-CD40x4-1BB (GEN1042/BNT312) Using a mPBPK/RO Model Leveraging Preclinical and Clinical Data.Clinical pharmacology and therapeutics · 2025Trial
- Teclistamab Dosing in Responders: Modeling and Simulation Results from the MajesTEC-1 Study in Relapsed/Refractory Multiple Myeloma.Targeted oncology · 2025Trial
- Translating B-Cell and Plasma-Cell Targeting from Oncology to Autoimmunity: Modalities, Quantitative Bridging, and a Development Roadmap.Clinical pharmacology and therapeutics · 2026Review
- PK-PD Modeling Suggests Tumor Heterogeneity Limits Preclinical to Clinical Translation of Enzalutamide in Prostate Cancer.Pharmaceutical research · 2026Article
- The claudin-18.2-CD3 bispecific antibody IBI389 exerts an antitumor effect on malignant tumors with positive claudin-18.2 expression by promoting T-cell infiltration and remodeling the tumor immune microenvironment.Translational cancer research · 2026Article
- OPTIMIS: Optimizing Personalized Therapies through Integrated Multiscale Intelligent Simulation.bioRxiv : the preprint server for biology · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- A Generalized Minimal PBPK-PD Model of Bispecific Antibodies: Case Studies and Applications in Drug Development.CPT: pharmacometrics & systems pharmacology · 2026Article
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity.The AAPS journal · 2025Article
- PD-1-Cis IL-2R Agonism Determines the Predicted Pharmacological Dose Range for the Immunocytokine Eciskafusp Alfa (PD1-IL2v).CPT: pharmacometrics & systems pharmacology · 2025Article
- Using Virtual Patients to Evaluate Dosing Strategies for Bispecifics With a Bell-Shaped Efficacy Curve.CPT: pharmacometrics & systems pharmacology · 2025Article
- Leveraging quantitative systems pharmacology modeling for elranatamab regimen optimization in relapsed or refractory multiple myeloma.NPJ systems biology and applications · 2025Article
- Development of a Heuristic Machine Analogy Method for Model Simplification With an Application to a Large-Scale Model of Gi/Gs Signaling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Model-Informed Selection of the Recommended Phase 2 Dosage for Anti-TIGIT Immunotherapy Leveraging co-Expressed PD-1 Inhibitor Target Engagement.Clinical pharmacology and therapeutics · 2025Article
- Whole-Body Physiologically Based Pharmacokinetic Modeling Framework for Tissue Target Engagement of CD3 Bispecific Antibodies.Pharmaceutics · 2025Article
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- Targeting CD200 in Breast Cancer: Opportunities and Challenges in Immunotherapeutic Strategies.International journal of molecular sciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD3 bispecific antibody constructs recruit cytolytic T cells to kill tumor cells, offering a potent approach to treat cancer. T cell activation is driven by the formation of a trimolecular complex (trimer) between drugs, T cells, and tumor cells, mimicking an immune synapse. A translational quantitative systems pharmacology (QSP) model is proposed for CD3 bispecific molecules capable of predicting trimer concentration and linking it to tumor cell killing. The model was used to quantify the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of a CD3 bispecific targeting P-cadherin (PF-06671008). It describes the disposition of PF-06671008 in the central compartment and tumor in mouse xenograft models, including binding to target and T cells in the tumor to form the trimer. The model incorporates T cell distribution to the tumor, proliferation, and contraction. PK/PD parameters were estimated for PF-06671008 and a tumor stasis concentration (TSC) was calculated as an estimate of minimum efficacious trimer concentration. TSC values ranged from 0.0092 to 0.064 pM across mouse tumor models. The model was translated to the clinic and used to predict the disposition of PF-06671008 in patients, including the impact of binding to soluble P-cadherin. The predicted terminal half-life of PF-06671008 in the clinic was approximately 1 day, and P-cadherin expression and number of T cells in the tumor were shown to be sensitive parameters impacting clinical efficacy. A translational QSP model is presented for CD3 bispecific molecules, which integrates in silico, in vitro and in vivo data in a mechanistic framework, to quantify and predict efficacy across species.
Indexed as
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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.