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微波消融联合 CAR-T 细胞治疗在荷瘤小鼠模型中的应用

英文原题:Combining Microwave Ablation With CAR-T-Cell Therapy in Tumor-Bearing Mouse Models.

查看英文原题

Combining Microwave Ablation With CAR-T-Cell Therapy in Tumor-Bearing Mouse Models.

PubMed 2025/10/20(内容时间) Bio Protoc Q3 · IF 1.3(JCR 2025)

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中文摘要

微波消融(MWA)是一种广泛用于局部肿瘤控制的热消融技术,还可能激发全身性抗肿瘤免疫。尽管单独使用MWA很少能够清除复发或转移性疾病,但其重塑肿瘤微环境的能力使其有望与嵌合抗原受体(CAR)T细胞等过继细胞疗法联合应用。

然而,目前这类联合方案的可重复操作流程仍有限。本方案介绍在荷瘤小鼠模型中联合实施MWA与CAR-T 治疗的方法。将人肝细胞癌细胞系Hep3B和SK-HEP-1皮下注射至NOG小鼠以建立肿瘤;采用可调节功率和时长的局部MWA,实现部分或完全消融。消融后在预定时间点,将健康供者T细胞经慢病毒转导制备的CAR-T 细胞静脉注入小鼠。这一实验设计将MWA与CAR-T 细胞递送分开,可精准评估热疗预处理对肿瘤微环境及后续CAR-T 活性的影响。该方案将局部消融与过继免疫治疗结合,为优化治疗时机、增强CAR-T 治疗实体瘤疗效,以及应对肿瘤免疫学和癌症治疗中的关键障碍,提供了具有转化意义的平台。主要特点:提供研究小鼠肿瘤模型中MWA与CAR-T 联合治疗的实用流程;详述肿瘤细胞制备、皮下注射、MWA治疗和CAR-T 细胞给药步骤;创新性地分开实施预处理与细胞给药,以便严格分析微环境预处理及治疗应答;对改善实体瘤CAR-T 疗法具有转化意义,可应对临床应用中的关键障碍。

展开英文摘要原文

Microwave ablation (MWA) is a thermal ablation technique widely used for local tumor control that has the added potential to stimulate systemic anti-tumor immunity. Although MWA alone rarely eliminates recurrent or metastatic disease, its ability to remodel the tumor microenvironment makes it a promising partner for adoptive cell therapies such as chimeric antigen receptor (CAR)-T cells.

However, reproducible protocols for combining these approaches remain limited. This protocol describes the integration of MWA with CAR-T therapy in tumor-bearing mouse models. Human hepatocellular carcinoma cell lines (Hep3B and SK-HEP-1) are inoculated subcutaneously into NOG mice to establish tumors. Localized MWA is performed at adjustable power and duration to induce partial or complete ablation. At defined intervals following MWA, CAR-T cells derived from healthy donor T cells and transduced with a lentiviral vector are injected intravenously. This experimental design uniquely separates MWA and CAR-T delivery, enabling precise evaluation of thermal preconditioning effects on the tumor microenvironment and subsequent CAR-T activity.

By combining localized ablation with adoptive immunotherapy, the protocol provides a translationally relevant platform to optimize treatment timing, enhance CAR-T efficacy in solid tumors, and address key barriers in tumor immunology and cancer therapy. Key features Practical protocol to investigate MWA and CAR-T-cell combination therapy in mouse tumor models.

Includes detailed procedures for tumor cell preparation, subcutaneous inoculation, MWA treatment, and CAR-T-cell administration. Novel protocol design separates MWA and CAR-T delivery, allowing rigorous analysis of preconditioning effects on the tumor microenvironment and therapy response. Offers translational relevance for improving CAR-T therapy in solid tumors, addressing a critical barrier to clinical application.

论文信息

作者
Cao B、Wheeler GL、Mast J、Zhao Q、Shen J
单位
Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN, USA.United States
期刊
Bio-protocol2025 Oct 20
原文标识
PubMed 41141638 · DOI 10.21769/BioProtoc.5470