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帕博利珠单抗联合 DC-CIK 细胞治疗晚期肝细胞癌:一例病例报告

英文原题:Combination treatment of pembrolizumab with DC-CIK cell therapy for advanced hepatocellular carcinoma: A case report.

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Combination treatment of pembrolizumab with DC-CIK cell therapy for advanced hepatocellular carcinoma: A case report.

PubMed 2023/09/01(内容时间) Biomedicine (Taipei) Q1 · IF 3(JCR 2025)

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研究概要

既往体内研究发现,联合免疫治疗可改善小鼠模型中的肿瘤控制。此外,在既往临床研究中,AFP 水平可能是肿瘤反应的替代标志物。因此,我们认为 AFP 水平下降更快是检查点抑制剂联合细胞治疗在 HCC 治疗中协同效应的临床证据。

研究思路结论见上方概要

近年来,免疫治疗已成为晚期HCC治疗的一种有前景的方法。已有若干关于免疫检查点抑制剂和免疫细胞治疗的临床试验和meta分析,但缺乏这两种治疗联合应用的临床证据。病例描述:一名66岁男性,患有慢性乙型肝炎相关肝硬化,因急性腹痛到某医院急诊科就诊。查体时,其腹部右上象限可触及肿块。增强腹部计算机断层扫描显示右叶有一个大肿瘤,大小为13 cm × 17 cm,并伴有右门静脉血栓形成。甲胎蛋白(AFP)水平为30,905 mg/dL。因此,该患者被诊断为BCLC C期肝细胞癌(HCC)。他接受了经动脉化疗栓塞(TACE)、腹部放疗、nivolumab和lenvatinib治疗。他的疾病一直得到控制,直到两年后,疾病进展并出现多发肺转移,其AFP水平从约1000升至17,000 ng/ml。在这一阶段,他于2022年1月接受了新的联合免疫治疗。他首先使用了pembrolizumab(100 mg),AFP水平每天下降600 ng/ml。然后,他在使用pembrolizumab两周后接受了DC-CIK细胞治疗,AFP水平每天下降至900 ng/ml。不幸的是,治疗后出现了严重肺炎和张力性气胸。患者拒绝接受进一步治疗,并平静地去世。

展开英文摘要原文

Recently, immunotherapy has emerged as a promising method for advanced HCC treatment. There are several clinical trials and meta-analyses of immune checkpoint inhibitors and immune cell therapy, but clinical evidence on the combination of these two therapies is lacking. CASE DESCRIPTION: A 66-year-old man with chronic hepatitis B-related cirrhosis complained of acute abdominal pain in an emergency department of a hospital. On exams, there was a palpable mass in the right upper quadrant of his abdomen. Contrast-enhanced abdominal computed tomography showed a large tumor in the right lobe, 13 cm × 17 cm in size, and right portal vein thrombosis. The alpha-fetoprotein (AFP) level was 30,905 mg/dL. Therefore this patient was diagnosed with BCLC stage C hepatocellular carcinoma (HCC). He underwent trans-arterial chemo-embolization (TACE), abdominal radiotherapy, nivolumab, and lenvatinib. His disease had been under control until two years later, the disease progressed with multiple lung metastases, and his AFP level rose from around 1000 to 17,000 ng/ml. At this stage, he underwent new combination immunotherapy in January 2022. He used pembrolizumab (100 mg) first, and the AFP level decreased by 600 ng/ml daily. Then he received DC-CIK cell therapy two weeks after using pembrolizumab, and the AFP level declined to 900 ng/ml a day. Unfortunately, severe pneumonitis and tension pneumothorax developed after therapy. The patient denied undergoing further treatment and expired peacefully.

The previous in-vivo study found that combination immunotherapy can improve tumor control in the mice model. Besides, in previous clinical studies, the level of AFP may be a surrogate marker of tumor response. Therefore we thought the more rapidly declined level of AFP was the clinical evidence of the synergistic effect of checkpoint inhibitors combined with cell therapy in HCC treatment.

论文信息

作者
Huang SM、Jeng LB、Shyu WC、Chen HY
第一作者单位
China Medical University Hospital, Taichung, Taiwan.China
通讯作者单位
Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.China
文献类型
病例报告
期刊
BioMedicine2023
原文标识
PubMed 37937058 · DOI 10.37796/2211-8039.1414