ArticleCPT: pharmacometrics & systems pharmacology2023
Mechanistically modeling peripheral cytokine dynamics following bispecific dosing in solid tumors.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 25 citations in OpenAlex.
- Revised Recommendations for Restarting Teclistamab Following Dose Delays: Insights from the MajesTEC-1 Study on Clinical Safety, and from Simulated Pharmacokinetics and Cytokine Dynamics.Targeted oncology · 2026Article
- Clinical Development of T-Cell Bispecific Antibodies: Review, Challenges, and Prospective Solutions in Solid Tumor.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Model-Informed Drug Development Applications and Opportunities in mRNA-LNP Therapeutics.Clinical pharmacology and therapeutics · 2025Review
- QSP-Copilot: An AI-Augmented Platform for Accelerating Quantitative Systems Pharmacology Model Development.CPT: pharmacometrics & systems pharmacology · 2025Article
- Bispecific Antibodies in Solid Tumors: Advances and Challenges.International journal of molecular sciences · 2025Review
- A Multiple-Model-Informed Drug-Development Approach for Optimal Regimen Selection of an Oncolytic Virus in Combination With Pembrolizumab.CPT: pharmacometrics & systems pharmacology · 2025Article
- Clinical Pharmacology of Cytokine Release Syndrome with T-Cell-Engaging Bispecific Antibodies: Current Insights and Drug Development Strategies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Identifying biomarkers for treatment of uveal melanoma by T cell engager using a QSP model.NPJ systems biology and applications · 2024Article
- Hyperthermia in Combination with Emerging Targeted and Immunotherapies as a New Approach in Cancer Treatment.Cancers · 2024Review
- Coupling quantitative systems pharmacology modelling to machine learning and artificial intelligence for drug development: itsFrontiers in systems biology · 2024Article
- Development of bispecific T cell engagers: harnessing quantitative systems pharmacology.Trends in pharmacological sciences · 2023Review
- Mechanistically modeling peripheral cytokine dynamics following bispecific dosing in solid tumors.CPT: pharmacometrics & systems pharmacology · 2023Article
- Role of pharmacometrics and systems pharmacology in facilitating efficient dose optimization in oncology.CPT: pharmacometrics & systems pharmacology · 2023Article
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Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bispecific antibodies exhibit proven clinical benefit, and many bispecifics are currently in clinical development for oncology. Cytokine release syndrome (CRS) is a common clinical adverse effect observed following CD3-based bispecific dosing. However, the pathophysiology of CRS is not fully understood, and no computational model mechanistically describing clinical cytokine dynamics following bispecific dosing in solid tumors exists. Here, a quantitative systems pharmacology (QSP) model describing peripheral clinical cytokine dynamics following bispecific dosing in solid tumors is presented. Using tebentafusp as a case study, a CD3-bispecific approved for uveal melanoma, the model successfully captures the dynamics of five cytokines. The QSP model was shown to predict observed phenomena, such as cytokine maximum concentration suppression using step-up dosing regimens and the importance of on-target off-tumor binding toward CRS and toxicity. Furthermore, the QSP model provides rationale for these biological phenomena based on dynamics of immune cell activation and desensitization in tumors and healthy tissues. Overall, the QSP model structure presented here serves as a basis to infer cytokine dynamics for other CD3-based bispecifics or tumor types by altering model parameters to capture the scenario of interest, supporting applications including dose selection, candidate nomination, and disease area selection.
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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.