ArticleCPT: pharmacometrics & systems pharmacology2014
A mechanistic, multiscale mathematical model of immunogenicity for therapeutic proteins: part 2-model applications.
Article in CPT: pharmacometrics & systems pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 47 citations in OpenAlex.
- Evaluating a Multiscale Mechanistic Model of the Immune System to Predict Human Immunogenicity for a Biotherapeutic in Phase 1.The AAPS journal · 2019Trial
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- Review: application and opportunities for machine learning and artificial intelligence in preclinical immunogenicity risk assessment.Frontiers in immunology · 2026Review
- Role of Antidrug Antibodies in Oncolytic Viral Therapy: A Dynamic Modelling Approach in Cancer Patients Treated with V937 Alone or in Combination.Clinical pharmacokinetics · 2025Article
- Mechanism-Based Modeling Approaches to Quantify the Effect of Immunogenicity on the Pharmacokinetics of Therapeutic Proteins in Drug Development.CPT: pharmacometrics & systems pharmacology · 2025Review
- A Semi-Mechanistic Mathematical Model of Immune Tolerance Induction to Support Preclinical Studies of Human Monoclonal Antibodies in Rats.Pharmaceutics · 2025Article
- IQ Survey Results on Current Industry Practices: Part 2-Quantitative Evaluations of Immunogenicity Assessment.Clinical pharmacology and therapeutics · 2025Review
- The Role of Cross-Institutional and Interdisciplinary Collaboration in Defining and Executing a Quantitative Systems Pharmacology Strategy.Handbook of experimental pharmacology · 2025Review
- Towards new approach methodologies for biological therapeutics: a novel model-informed metric to assess immunogenicity risk.Frontiers in immunology · 2025Article
- The dawn of biophysical representations in computational immunology.QRB discovery · 2025Review
- Assessing the performance of QSP models: biology as the driver for validation.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- SAAM II: A general mathematical modeling rapid prototyping environment.CPT: pharmacometrics & systems pharmacology · 2024Article
- QSP Designer: Quantitative systems pharmacology modeling with modular biological process map notation and multiple language code generation.CPT: pharmacometrics & systems pharmacology · 2023Article
- Learn-confirm in model-informed drug development: Assessing an immunogenicity quantitative systems pharmacology platform.CPT: pharmacometrics & systems pharmacology · 2023Article
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Application of quantitative systems pharmacology to guide the optimal dosing of COVID-19 vaccines.CPT: pharmacometrics & systems pharmacology · 2021Article
- Current and prospective computational approaches and challenges for developing COVID-19 vaccines.Advanced drug delivery reviews · 2021Review
- QSP-IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno-Oncology Applications.CPT: pharmacometrics & systems pharmacology · 2020Article
- Integration of Omics Data Sources to Inform Mechanistic Modeling of Immune-Oncology Therapies: A Tutorial for Clinical Pharmacologists.Clinical pharmacology and therapeutics · 2020Review
- Immunogenicity in Clinical Practice and Drug Development: When is it Significant?Clinical and translational science · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A mechanistic, multiscale mathematical model of immunogenicity for therapeutic proteins was built by recapitulating key underlying known biological processes for immunogenicity. The model is able to simulate immune responses based on protein-specific antigenic properties (e.g., number of T-epitopes and their major histocompatibility complex (MHC)-II binding affinities) and host-specific immunological/physiological characteristics (e.g., MHC-II allele genotype, drug clearance rate). Preliminary validation was performed using mouse studies with antigens such as ovalbumin (OVA) or OVA-derived peptide. Further, using adalimumab as an example therapeutic protein, the model is able to simulate immune responses against adalimumab in individual subjects and in a population, and also provides estimations of immunogenicity incidence and drug exposure reduction that can be validated experimentally. This is a first attempt at modeling immunogenicity of biologics, so the model simulations should be used to help understand the immunogenicity mechanisms and impacting factors, rather than making direct predictions. This prototype model needs to be subjected to extensive experimental validation and refinement before fulfilling its ultimate mission of predicting immunogenicity. Nevertheless, the current model could potentially set up the starting framework to integrate various in silico, in vitro, in vivo, and clinical immunogenicity assessment results to help meet the challenge of immunogenicity prediction.
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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.