Intratumoural GM-CSF microspheres and CTLA-4 blockade enhance the antitumour immunity induced by thermal ablation in a subcutaneous murine hepatoma model
Intratumoural GM-CSF microspheres and CTLA-4 blockade enhance the antitumour immunity induced by thermal ablation in a subcutaneous murine hepatoma model
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DOI：
10.1080/02656730902976807
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发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Tao, Jianpin
中科院分区：
文献类型：
--
作者：
Chen, Zubing;Shen, Shiqiang;Tao, Jianpin
目的：我们评估了一种新的抗肿瘤免疫方案的效果，该方案包括微波消融、瘤内微球包封粒细胞-巨噬细胞集落刺激因子（GM-CSF）和细胞毒性t淋巴细胞相关抗原4 （CTLA-4）的阻断。材料和方法：C57BL6小鼠皮下Hepa 1-6肝癌，微波消融后瘤内注射GM-CSF微球，腹腔注射抗ctla -4抗体。通过肿瘤生长、生存分析和T淋巴细胞对Hepa 1-6的细胞毒性来评估治疗效果。结果：在皮下小鼠Hepa 1-6模型中，微波热消融、GM-CSF微球和抗ctla -4联合给药可使90%的治疗小鼠的肿瘤再攻击被拒绝，50%的治疗小鼠治愈了已建立的远处肿瘤。这种抗肿瘤免疫反应是肿瘤特异性的，由自然杀伤细胞（NK）、CD4+和CD8+T细胞介导。结论：微波消融，肿瘤内GM-CSF微球和抗ctla -4抗体导致肿瘤局部根除，肿瘤再攻击后的排斥反应，并治愈已建立的远处肿瘤，这表明这是一种很有前途的方案，很容易应用于临床。
Purpose: We evaluated the effect of a new antitumour immunity regimen that included microwave ablation, intratumoural microspheres encapsulating granulocyte-macrophage colony stimulating factor (GM-CSF), and blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).Materials and methods: C57BL6 mice with an established subcutaneous Hepa 1-6 hepatoma underwent microwave ablation, followed by intratumoural injection of GM-CSF microspheres, and intraperitoneal injection of anti-CTLA-4 antibodies. The therapeutic effects were evaluated by tumour growth, survival analysis, and cytotoxicity of T lymphocytes against Hepa 1-6.Results: The co-administration of microwave thermal ablation, GM-CSF microspheres, and anti-CTLA-4 rejected tumour rechallenge in 90% of treated mice in a subcutaneous murine Hepa 1-6 model, and cured established distant tumour in 50% of the treated mice. This antitumour immune response was tumour-specific and mediated by natural killer (NK), CD4+, and CD8+T cells.Conclusions: Microwave ablation, followed by intratumoural GM-CSF microspheres, and anti-CTLA-4 antibodies results in the local eradication of tumours, rejection of tumours following rechallenge, and cures established distant tumours, suggesting that this is a promising regimen and one that is readily applicable in the clinic.