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Mathematical modeling of endogenous and exogenously administered T cell recirculation in mouse and its application to pharmacokinetic studies of cell therapiesстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 декабря 2024 г.
- Авторы: Nikitich A., Helmlinger G., Peskov K., Bocharov G.
- Журнал: Frontiers in immunology
- Том: 15
- Год издания: 2024
- Издательство: Frontiers Research Foundation]
- Местоположение издательства: [Lausanne, Switzerland
- Первая страница: 1
- Последняя страница: 17
- Номер статьи: 1357706
- DOI: 10.3389/fimmu.2024.1357706
- Аннотация: Introduction: In vivo T cell migration has been of interest to scientists for the past 60 years. T cell kinetics are important in the understanding of the immune response to infectious agents. More recently, adoptive T cell therapies have proven to be a most promising approach to treating a wide range of diseases, including autoimmune and cancer diseases, whereby the characterization of cellular kinetics represents an important step towards the prediction of therapeutic efficacy.Methods: Here, we developed a physiologically-based pharmacokinetic (PBPK) model that describes endogenous T cell homeostasis and the kinetics ofexogenously administered T cells in mouse. Parameter calibration was performed using a nonlinear fixed-effects modeling approach based onpublished data on T cell kinetics and steady-state levels in different tissues of mice. The Partial Rank Correlation Coefficient (PRCC) method was used to perform a global sensitivity assessment. To estimate the impact of kinetic parameters on exogenously administered T cell dynamics, a local sensitivity analysis was conducted.Results: We simulated the model to analyze cellular kinetics following various Tcell doses and frequencies of CCR7+ T cells in the population of infusedlymphocytes. The model predicted the effects of T cell numbers and ofpopulation composition of infused T cells on the resultant concentration of Tcells in various organs. For example, a higher percentage of CCR7+ T cells amongexogenously administered T lymphocytes led to an augmented accumulation ofT cells in the spleen. The model predicted a linear dependence of T cell dynamicson the dose of adoptively transferred T cells.
- Добавил в систему: Бочаров Геннадий Алексеевич