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claudin18.2 靶向 CAR-T 细胞治疗诱导晚期胰腺癌完全缓解:一例病例报告

英文原题:Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report.

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Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report.

PubMed 2024/02/29(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

胰腺癌(PC)因其高度侵袭性和转移特性,是消化系统中最恶性的肿瘤之一。目前,PC的常规治疗策略临床疗效有限。因此,迫切需要新的有效治疗策略。

在此,我们报告一例由claudin18.2靶向CAR-T 细胞疗法诱导的晚期PC完全缓解病例。该患者为一名72岁男性,2年前被诊断为胰腺导管腺癌,在胰十二指肠切除术和多线化疗后出现肿瘤复发和多发转移,包括肝、腹膜和颈部淋巴结转移。随后,患者被转诊至我科进一步治疗转移性PC,并入组了一项claudin18.2靶向CAR-T 细胞疗法的临床试验。在淋巴细胞清除性化疗后,患者于2022年11月21日接受了剂量为1.2 10 6 cells/kg的claudin18.2靶向CAR-T 细胞输注。在CAR-T 细胞治疗期间,患者出现了2级细胞因子释放综合征(CRS)和胃黏膜损伤,经托珠单抗及常规对症支持治疗得到控制。患者在claudin18.2靶向CAR-T 细胞治疗后1个月达到完全缓解(CR),并维持临床缓解8个月。不幸的是,患者于2023年7月出现claudin18.2阴性复发。尽管在claudin18.2靶向CAR-T 细胞输注后出现抗原阴性复发,但患者获得了持续8个月的缓解,这表明claudin18.2靶向CAR-T 细胞疗法是治疗晚期PC的一种极其有效的治疗策略。

展开英文摘要原文

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy.

Therefore, novel effective therapeutic strategies are urgently needed.

Here, we report a case of complete remission of advanced PC induced by claudin18. 2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18. 2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18. 2-targeted CAR-T cell infusion at a dose of 1. 2 10 6 cells/kg on November 21, 2022.

During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18. 2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months.

Unfortunately, the patient experienced claudin18. 2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18. 2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18. 2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.

论文信息

作者
Zhong G、Zhang X、Guo Z、Gao Y、Zhao B、Liu X、Chen L、Qiao J
单位
Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.China
文献类型
病例报告 · 非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 38487523 · DOI 10.3389/fimmu.2024.1325860