CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
抗血管生成治疗增强 CAR-T 细胞在实体瘤中的疗效：来自混合多尺度模型的启示
英文原题：Antiangiogenic therapy enhances CAR-T cell efficacy in solid tumors: Insights from a hybrid multiscale model.
查看英文原题
Antiangiogenic therapy enhances CAR-T cell efficacy in solid tumors: Insights from a hybrid multiscale model.
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研究概要
我们的结果为抗血管生成联合 CAR-T 细胞疗法的治疗动态提供了深刻见解。
中文摘要
背景与目的
嵌合抗原受体（CAR）T 细胞在血液系统恶性肿瘤中疗效显著，但在实体瘤中的治疗效果仍有限，主要原因是 CAR-T 细胞浸润不足以及免疫抑制性肿瘤微环境（TME）。近期小鼠研究表明，抗血管生成治疗可提高 CAR-T 疗效，但仍需大量研究阐明其机制并制定有效治疗方案。
方法
研究建立一种混合离散-连续多尺度计算模型，用于研究实体瘤生长、血管生成和 CAR-T 细胞浸润。模型考虑静脉输注 CAR-T 细胞、其穿越内皮外渗以及在 TME 中发挥细胞毒作用的过程，因此可用于稳健研究抗血管生成治疗对 CAR-T 疗效的影响。
结果
模型结果显示，抗血管生成治疗可增强 CAR-T 细胞向实体瘤的递送并提高疗效。研究进一步评估不同治疗方案。结果表明，辅助和新辅助抗血管生成治疗均可改善结局，但新辅助方案带来更高生存率。此外，模型提出了一种可最大化生存的最佳给药时间表。
结论
研究结果深入揭示了抗血管生成治疗与 CAR-T 联合治疗的动态机制，并建立了可用于为临床试验选择治疗方案的计算框架。
展开英文摘要原文
METHODS
Here, we developed a hybrid discrete - continuous multi-scale computational model to study solid tumor growth, angiogenesis, and CAR-T cell infiltration. Our model considers the intravenous infusion of CAR-T cells, their extravasation through the endothelium, and their cytotoxic effect in the TME. Therefore, this model enables us to robustly investigate the impact of anti-angiogenic therapy on the efficacy of CAR-T cells.
RESULTS
Our findings showed that anti-angiogenic therapy enhances the delivery and efficacy of CAR-T cells in solid tumors. Subsequently, we evaluated different therapeutic regimens. The results revealed that although both adjuvant and neoadjuvant anti-angiogenic therapy can improve outcome, the neoadjuvant regimen yields higher survival rates. Moreover, our model suggested an optimal dosing schedule to maximize survival.
CONCLUSIONS
Our results provide profound insight into the therapeutic dynamics of combined anti-angiogenic and CAR-T cell therapy. Additionally, the model establishes a computational framework for selecting treatment regimens for clinical trials.
论文信息
- 作者
- Mortazavi SMA、Firoozabadi B
- 第一作者单位
- Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran.Iran
- 通讯作者单位
- Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran. Electronic address: firoozabadi@sharif.edu.Iran
- 期刊
- Computer methods and programs in biomedicine2026 Aug 15
- 原文标识
- PubMed 42139795 · DOI 10.1016/j.cmpb.2026.109434