GPC3-IL7-CCL19-CAR-T主要用于肝细胞癌治疗的免疫微环境复制
Li-Li Lu1,2, Shu-Xiu Xiao1,2, Zhi-Yuan Lin3
1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
Cell biology and toxicology
|October 18, 2023
概括
新型GPC3-7-19-CAR-T细胞通过增强T细胞功能和逆转瘤微环境,提高了治疗肝细胞癌 (HCC) 的疗效. 这种先进的仿真抗原受体 (CAR) -T细胞疗法在临床试验中显示出有前途的安全性和抗瘤作用.
科学领域:
- 免疫治疗是一种免疫疗法.
- 在瘤学瘤学.
- 细胞疗法细胞疗法
背景情况:
- 化学抗原受体 (CAR) -T细胞疗法是晚期癌症的关键治疗方法.
- 传统的glypican-3 (GPC3) -CAR-T细胞在晚期肝细胞癌 (HCC) 中显示出有限的疗效.
- 传统GPC3-CAR-T细胞在HCC治疗中的有限疗效背后的机制尚未完全理解.
研究的目的:
- 评估新型GPC3-7-19-CAR-T细胞在治疗晚期HCC的临床效用.
- 探索GPC3-7-19-CAR-T细胞增强抗瘤作用的基础机制.
- 在I期临床试验中评估GPC3-7-19-CAR-T细胞的安全性和有效性.
主要方法:
- 设计的新型GPC3向的CAR-T细胞 (GPC3-7-19-CAR-T) 与IL-7和CCL19共同表达.
- 通过细胞杀死试验和3D微流体芯片HCC器官模型在体外验证有效性.
- 在人性化NSG小鼠异种移植模型中评估了体内抗瘤能力,并启动了I期临床试验.
主要成果:
- 与传统的GPC3-7-19-CAR-T细胞相比,GPC3-7-19-CAR-T细胞的杀死效率高1.5至2倍.
- 在体内研究显示,GPC3-7-19-CAR-T组的瘤形成率降低,瘤体积较小.
- 治疗导致CD4+ T_EM和CD8+ T_CM细胞的透增加,逆转了免疫抑制性瘤微环境,并减少了调控性T细胞和骨髓系衍生抑制细胞.
结论:
- 通过特定的T细胞子集重建瘤微环境,GPC3-7-19-CAR-T细胞表现出优异的抗瘤作用.
- 新型CAR-T细胞成功地招募了树突细胞,增强了杀死GPC3+ HCC细胞的能力.
- 在先进的HCC患者中,GPC3-7-19-CAR-T细胞显示出良好的安全性和抗瘤疗效,提供了一个有前途的治疗策略.
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