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从 T 细胞制造药物:工程化 T 细胞治疗产品的定量药理学

英文原题:Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics.

查看英文原题

Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics.

PubMed 2024/03/18(内容时间) NPJ Syst Biol Appl Q1 · IF 4.4(JCR 2025)

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中文摘要

工程化T细胞已成为血液系统恶性肿瘤的高效治疗方法。目前有数百项临床项目正在推进,旨在拓展这一免疫治疗模式的疗效、安全性和应用范围。开发这些“活体药物”面临的一个主要挑战是其药理学的复杂性,因为药物产品会增殖、分化、在组织间转运,并通过与患者免疫系统的相互作用而演变。利用来自嵌合抗原受体(CAR)T细胞的公开临床数据,我们展示了如何运用数学模型来量化产品特征、患者生理学、药代动力学与临床结局之间的关系。随着科学家致力于开发下一代细胞治疗产品,数学模型将成为整合数据背景、促进产品设计向临床策略转化的关键工具。

展开英文摘要原文

Engineered T cells have emerged as highly effective treatments for hematological cancers. Hundreds of clinical programs are underway in efforts to expand the efficacy, safety, and applications of this immuno-therapeutic modality. A primary challenge in developing these "living drugs" is the complexity of their pharmacology, as the drug product proliferates, differentiates, traffics between tissues, and evolves through interactions with patient immune systems.

Using publicly available clinical data from Chimeric Antigen Receptor (CAR) T cells, we demonstrate how mathematical models can be used to quantify the relationships between product characteristics, patient physiology, pharmacokinetics and clinical outcomes. As scientists work to develop next-generation cell therapy products, mathematical models will be integral for contextualizing data and facilitating the translation of product designs to clinical strategy.

论文信息

作者
Kirouac DC、Zmurchok C、Morris D
单位
Notch Therapeutics, Vancouver, BC, Canada. daniel.kirouac@ubc.ca.Canada
期刊
NPJ systems biology and applications2024 Mar 18
原文标识
PubMed 38499572 · DOI 10.1038/s41540-024-00355-3