RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
恒定自然杀伤 T 细胞输注联合经动脉栓塞 vs 单纯经动脉栓塞治疗肝细胞癌患者的疗效：一项 2 期随机临床试验
英文原题：Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial.
查看英文原题
Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
iNKT 细胞输注在 TAE 治疗 HCC 患者期间显著改善了 PFS、ORR、DCR 和 QoL，毒性可控。试验注册 ClinicalTrials.gov 标识符：NCT04011033。
研究思路结论见上方概要
目的
恒定NKT细胞（iNKT）是CD1d限制性T细胞，具有抗肿瘤免疫能力。自体iNKT细胞治疗肝细胞癌（HCC）的安全性已得到验证。本研究旨在探讨其在经动脉化疗栓塞（TACE）失败后晚期HCC中的疗效。
方法
这项开放标签、随机、对照试验在三个中心纳入了60例TACE失败后不可切除的HCC患者。采用经动脉栓塞（TAE）替代TACE以保护iNKT细胞功能。患者按1:1随机分配接受TAE治疗联合（TAE-iNKT）或不联合（TAE）每两周一次的iNKT细胞输注。主要终点为无进展生存期（PFS）。次要终点包括总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）、生活质量（QoL）、外周血细胞计数和安全性。
结果
54例患者完成了研究。TAE-iNKT患者的中位PFS显著高于TAE患者（5.7个月[95% CI，4.3-7.0个月] vs 2.7个月[95% CI，2.3-3.2个月]；风险比0.32[95% CI，0.16-0.63]；P <0.001）。TAE-iNKT患者的ORR和DCR均高于TAE患者（分别为52%和85% vs 11%和33%）。5例TAE-iNKT患者和1例TAE患者达到完全缓解。TAE-iNKT患者QoL恶化的中位时间长于TAE患者（9.2个月[95% CI，6.0-13.3个月] vs 3.0个月[95% CI，2.9-3.0个月]）。TAE-iNKT组在第8周（1.48 vs 0.95×10 9 /L，P = 0.007）和第12周（1.49 vs 0.89×10 9 /L，P = 0.001）的平均淋巴细胞计数均高于TAE组。3级不良事件发生于1例TAE-iNKT患者（4%）和5例TAE患者（19%）。所有其他不良事件均为1-2级。
展开英文摘要原文
PURPOSE
Invariant NKT cells (iNKT) are CD1d-restricted T cells with the capacity of antitumor immunity. The safety of autologous iNKT cell treatment in hepatocellular carcinoma (HCC) has been verified. This study aimed to investigate its efficacy in advanced HCC after transarterial chemoembolization (TACE) failure.
PATIENTS AND METHODS
This open-label, randomized, controlled, trial enrolled 60 patients with unresectable HCC after TACE failure at three centers. Transarterial embolization (TAE) was used instead of TACE to protect iNKT cell function. Patients were randomly assigned (1:1) to receive TAE therapy with (TAE-iNKT) or without (TAE) biweekly iNKT cell infusion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety.
RESULTS
Fifty-four patients completed the study. Median PFS was significantly higher in TAE-iNKT patients (5.7 months [95% CI, 4.3-7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3-3.2 months]; hazard ratio 0.32 [95% CI, 0.16-0.63]; P <0.001). Higher ORR and DCR were observed in TAE-iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively). Five TAE-iNKT patients and 1 TAE patient achieved completed response. The median time to deterioration in QoL was longer in TAE-iNKT patients (9.2 months [95% CI, 6.0-13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9-3.0 months]). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs 0.95×10 9 /L, P = 0.007) and 12 (1.49 vs 0.89×10 9 /L, P = 0.001) weeks. Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All the other adverse events were grade 1-2.
CONCLUSION
iNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC. Trial Registration ClinicalTrials.gov Identifier: NCT04011033.
论文信息
- 作者
- Guo J、Bao X、Liu F、Guo J、Wu Y、Xiong F、Lu J
- 单位
- Hepatology and Cancer Biotherapy Ward, Beijing YouAn Hospital, Capital Medical University, Beijing, People's Republic of China.China
- 文献类型
- 病例报告 · 临床试验
- 期刊
- Journal of hepatocellular carcinoma2023
- 原文标识
- PubMed 37637501 · DOI 10.2147/JHC.S416933
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