一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer.
The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer.
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射频消融(RFA)是一种在影像引导下利用射频热效应诱导肿瘤组织凝固性坏死的技术。然而,肿瘤血管生成导致的肿瘤细胞远处转移可导致肿瘤清除不彻底。
本研究采用LLC1细胞系构建皮下异种移植瘤。每2天灌胃给予10 mg/kg或20 mg/kg Fosbretabulin disodium(FBTD),持续一周。用药结束时进行RFA。通过流式细胞术检测T细胞比例。通过ELISA检测小鼠血清IgG和IgA水平。通过qRT-PCR assay评估特定基因的表达。
在本研究中,我们证明FBTD能够通过上调RFA诱导的CD8+杀伤性T细胞,显著增强荷瘤小鼠中RFA诱导的免疫功能。一致地,与单独RFA组或单独FBTD组相比,10 mg/kg或20 mg/kg FBTD治疗上调了荷瘤小鼠中IFNγ+和TNFα+ CD8+TIL(肿瘤浸润淋巴细胞)的百分比。在机制上,我们报道FBTD在体内抑制了RFA诱导的PD-1和PD-L1上调。
总之,我们在本研究中证明FBTD促进了RFA在荷瘤小鼠中的抗肿瘤效果。
Radiofrequency ablation (RFA) is a technology that uses radiofrequency thermal effect to induce coagulation necrosis of tumor tissue under the guidance of imaging.
However, distant metastasis of tumor cells caused by tumor angiogenesis can lead to incomplete tumor clearing. In this study, LLC1 cell line was used for the construction of subcutaneous xenografts. Either 10 mg/kg or 20 mg/kg Fosbretabulin disodium (FBTD) was intragastrically administered every 2 days for a week. RFA was performed at the end of medication. The proportion of T cells was examined by flow cytometry. Serum IgG and IgA levels of mice were examined by ELISA.
Expression of certain genes was estimated by qRT-PCR assay. In this study, we demonstrated that FBTD was able to significantly enhance RFA-induced immune function in tumor-bearing mice by upregulating RFA-induced CD8+ killer T cells. Consistently, 10 mg/kg or 20 mg/kg FBTD therapy upregulated the percentage of IFNγ+ and TNFα+ CD8+ tumor infiltrating lymphocytes in tumor-bearing mice compared to the RFA alone or FBTD alone group.
Mechanistically, we reported that FBTD inhibited the RFA-induced PD-1 and PD-L1 upregulation in vivo.
In conclusion, we demonstrated that FBTD promoted the antitumor effects of RFA in lung tumor-bearing mice in this study.
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