ArticleeLife2023
Population dynamics of immunological synapse formation induced by bispecific T cell engagers predict clinical pharmacodynamics and treatment resistance.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 21 citations in OpenAlex.
- T-cell Receptor (TCR) Targeting with Multivalent T-cell Engagers.bioRxiv : the preprint server for biology · 2026Article
- Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Targeting the immunological synapse in multiple myeloma.Discover oncology · 2026Review
- Molecular Mechanisms of Resistance to Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.Cells · 2026Review
- Enhancement of CD117-Targeted Bispecific T-cell Engagement by CD33-Targeted Bispecific T-cell Costimulation in Acute Myeloid Leukemia.Cancer research communications · 2026Article
- Blinatumomab-driven T-cell activation in αβ and γδ T-cell subsets: insights fromFrontiers in immunology · 2026Article
- An Overview on T-Cell Engagers: The Current Position in Both the Biological and Mathematical Context.Computational and structural biotechnology journal · 2026Review
- Overview of Quantitative Clinical Pharmacology for T-Cell Engaging Bispecific Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity.The AAPS journal · 2025Article
- Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- T-Cell Engager Therapy in Prostate Cancer: Molecular Insights into a New Frontier in Immunotherapy.Cancers · 2025Review
- Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Article
- Functional Activity of Cytokine-Induced Killer Cells Enhanced by CAR-CD19 Modification or by Soluble Bispecific Antibody Blinatumomab.Antibodies (Basel, Switzerland) · 2024Article
- Optimizing Clinical Translation of Bispecific T-cell Engagers through Context Unification with a Quantitative Systems Pharmacology Model.Clinical pharmacology and therapeutics · 2024Article
- Design of Crosslinking Antibodies For T-Cell Activation: Experimental and Computational Analysis of PD-1/CD137 Bispecific Agents.The AAPS journal · 2024Article
- Realizing the promise of Project Optimus: Challenges and emerging opportunities for dose optimization in oncology drug development.CPT: pharmacometrics & systems pharmacology · 2024Review
- A Proximity-Dependent Biosensor System for Visualizing Cell-Cell Interactions Induced by Therapeutic Antibodies.Journal of pharmaceutical sciences · 2024Article
- Development of bispecific T cell engagers: harnessing quantitative systems pharmacology.Trends in pharmacological sciences · 2023Review
- Decoding the Complexity of Immune-Cancer Cell Interactions: Empowering the Future of Cancer Immunotherapy.Cancers · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Effector T cells need to form immunological synapses (IS) with recognized target cells to elicit cytolytic effects. Facilitating IS formation is the principal pharmacological action of most T cell-based cancer immunotherapies. However, the dynamics of IS formation at the cell population level, the primary driver of the pharmacodynamics of many cancer immunotherapies, remains poorly defined. Using classic immunotherapy CD3/CD19 bispecific T cell engager (BiTE) as our model system, we integrate experimental and theoretical approaches to investigate the population dynamics of IS formation and their relevance to clinical pharmacodynamics and treatment resistance. Our models produce experimentally consistent predictions when defining IS formation as a series of spatiotemporally coordinated events driven by molecular and cellular interactions. The models predict tumor-killing pharmacodynamics in patients and reveal trajectories of tumor evolution across anatomical sites under BiTE immunotherapy. Our models highlight the bone marrow as a potential sanctuary site permitting tumor evolution and antigen escape. The models also suggest that optimal dosing regimens are a function of tumor growth, CD19 expression, and patient T cell abundance, which confer adequate tumor control with reduced disease evolution. This work has implications for developing more effective T cell-based cancer immunotherapies.
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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.