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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Combining Microwave Ablation With CAR-T-Cell Therapy in Tumor-Bearing Mouse Models.
Combining Microwave Ablation With CAR-T-Cell Therapy in Tumor-Bearing Mouse Models.
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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。
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.
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