肿瘤细胞治疗研究
英文原题：A phase I trial of combination CAR-NK92MI immunotherapy by dual targeting MUC-1 and PD-L1 for patients with relapsed or refractory solid tumors: focus on non-small cell lung cancer.
我们的结果表明，MUC-1 与 PD-L1 联合靶向的 CAR-NK92MI 细胞疗法是治疗伴转移的复发/难治性非小细胞肺癌患者的安全有效方法。
背景：NK92MI细胞是肿瘤免疫治疗中一种特征明确的自然杀伤（NK）细胞系。本研究考察靶向MUC-1和PD-L1的嵌合抗原受体NK92MI（CAR-NK92MI）细胞联合疗法治疗晚期非小细胞肺癌（NSCLC）的效果。材料与方法：2016至2018年，7例复发或难治性NSCLC患者参加该临床试验（ClinicalTrials.gov编号NCT02839954，注册日期为2016年7月21日）。患者接受按1:1比例混合的MUC-1和PD-L1 CAR-NK92MI细胞输注，单次剂量为1×10^8至2×10^9个CAR-NK92MI细胞。输注次数为3至37次，中位数为22次。除非出现无法耐受的毒性或疾病进展（PD），所有患者均在1年内完成CAR-NK92MI细胞输注。结果：7例患者均能良好耐受治疗。未观察到CAR-NK92MI治疗相关细胞因子释放综合征（CRS）或严重不良事件。7例中有3例达到疾病稳定，持续超过23个月。自初次治疗起，无进展生存期（PFS）中位数为12个月（范围2–60个月），总生存期（OS）中位数为19个月（范围3–60个月）。结论：结果表明，联合靶向MUC-1和PD-L1的CAR-NK92MI细胞疗法对于伴转移的复发难治性NSCLC患者是一种安全有效的方法。本研究已于2016年7月21日在ClinicalTrials.gov注册（NCT02839954）。
BACKGROUND: NK92MI cells are well-defined natural killer (NK) cell lines for tumor immunotherapy. In this study, we investigated a combination therapy of MUC-1 and PD-L1 targeted chimeric antigen receptor NK92MI (CAR-NK92MI) cells for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 2016 to 2018, 7 patients with relapsed or refractory NSCLC were included in this clinical trial (ClinicalTrials.gov number, NCT02839954.Registered in 21/07/2016.). 1:1 mixed MUC-1 and PD-L1 CAR-NK92MI cells were infused, and the dosage was set at 1 108 to 2 109 CAR-NK92MI cells once. The infusion times were ranged from 3 to 37, and the median time were 22. All patients completed CAR-NK92MI cells infusion within 1 year unless intolerable toxicities appeared or disease progression (PD) occurred. RESULTS: All 7 patients were well-tolerated in the treatment. No cytokine release syndrome (CRS) and serious adverse events related to CAR-NK92MI treatment were observed. 3/7 patients achieved stable disease within more than 23 months. The median progression-free survival (PFS) was 12 months (2 to 60months) from the initial treatment, and the median overall survival (OS) was 19 months (3 to 60 months). CONCLUSION: Our results demonstrated that the combined MUC-1 and PD-L1 targeted CAR-NK92MI cell therapy is safe and efficient approach for relapsed and refractory NSCLC patients with metastasis. TRIAL REGISTRATION: Our study was registered in ClinicalTrials.gov ( https://classic.clinicaltrials.gov/ ) (NCT02839954) in 21/07/2016.
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