ArticleInternational journal of molecular sciences2021
A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Trial
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- CAR T-cell and oncolytic virus dynamics and determinants of combination therapy success for glioblastoma.Mathematical biosciences · 2025Article
- Spatiotemporal dynamics of tumor-CAR T-cell interaction following local administration in solid cancers.PLoS computational biology · 2025Article
- Mathematical modeling unveils the timeline of CAR-T cell therapy and macrophage-mediated cytokine release syndrome.PLoS computational biology · 2025Article
- Computational modelling of CAR T-cell therapy: from cellular kinetics to patient-level predictions.EBioMedicine · 2025Review
- Mathematical Model of CAR T-Cell Therapy for a B-Cell Lymphoma Lymph Node.Bulletin of mathematical biology · 2025Article
- Mathematical models and computational approaches in CAR-T therapeutics.Frontiers in immunology · 2025Review
- Bispecific antibody (ABL602 2 + 1) induced bistable acute myeloid leukemia kinetics.Scientific reports · 2024Article
- Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics.NPJ systems biology and applications · 2024Article
- Deconvolution of clinical variance in CAR-T cell pharmacology and response.Nature biotechnology · 2023Article
- Immunological Responses to Cancer Therapy.International journal of molecular sciences · 2022Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.
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