Journal article
Applying population mechanistic modelling to find determinants of chimeric antigen receptor T-cells dynamics in month-one lymphoma patients
- Abstract:
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Background: Chimeric antigen receptor (CAR) T-cells have been utilized for the treatment of several malignancies, including Non-Hodgkin lymphomas. A myriad of product- and patient-specific factors determines the extent of patient response, and determining which are most impactful requires analysis of clinical data.
Methods: We used population-level ordinary differential equation models to fit clinical flow cytometry and tumour biopsy data from the TRANSCEND-NHL-001 (NCT02631044) study [1]. We analyzed the impact of lymphodepletion, CAR T-cell phenotypes, and other factors on CAR T-cell dynamics for 30 days after infusion.
Results: We quantified the relative contribution of antigen-dependent and independent sources of proliferation on CAR T-cell dynamics, finding that both make a large contribution and that antigen-independent proliferation was highly correlated with patient IL-15 and IL-7 blood concentrations. The proportion of CAR T-cells in naïve, memory, or effector cells was found to have a limited impact on CAR T-cell dynamics, compared with lymphodepletion and tumour burden.
Conclusions: This study shows how models can be used to link endogenous T-cells, CAR T-cells, and their phenotypes, and may be useful for determining whether a given patient may be responding poorly to treatment, by observing the dynamics of their endogenous T-cells. The framework we developed can be utilized for other CAR T constructs and indications, to test product alterations or biological hypotheses at the population level.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 11.0MB, Terms of use)
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- Publisher copy:
- 10.1093/immadv/ltaf001
Authors
- Publisher:
- Oxford University Press
- Journal:
- Immunotherapy Advances More from this journal
- Volume:
- 5
- Issue:
- 1
- Article number:
- ltaf001
- Publication date:
- 2025-06-09
- Acceptance date:
- 2024-11-24
- DOI:
- EISSN:
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2732-4303
- Language:
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English
- Keywords:
- Pubs id:
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2067440
- Local pid:
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pubs:2067440
- Deposit date:
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2024-11-28
Terms of use
- Copyright holder:
- Brown et al
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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