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.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China.
Front Immunol. 2024 Feb 29;15:1325860. doi: 10.3389/fimmu.2024.1325860. eCollection 2024.
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 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.
胰腺癌（PC）是消化系统中最恶性的肿瘤之一，因其具有高度侵袭性和转移性。目前，PC 的常规治疗策略显示出有限的临床疗效。因此，迫切需要新的有效治疗策略。在这里，我们报告了一例 Claudin18.2 靶向 CAR-T 细胞治疗诱导的晚期 PC 完全缓解的病例。患者为 72 岁男性，2 年前被诊断为胰腺导管腺癌，胰十二指肠切除术和多线化疗后（包括肝、腹膜和颈部淋巴结转移）发生肿瘤复发和多处转移。随后，患者被转至我科进一步治疗转移性 PC，并被纳入 Claudin18.2 靶向 CAR-T 细胞治疗的临床试验。在淋巴清除化疗后，患者于 2022 年 11 月 21 日接受了 1.2×10 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 2 级细胞因子释放综合征（CRS）和胃黏膜损伤，经托珠单抗和常规对症支持治疗得到控制。Claudin18.2 靶向 CAR-T 细胞治疗后 1 个月，患者达到完全缓解（CR），并保持临床缓解 8 个月。不幸的是，患者于 2023 年 7 月出现 Claudin18.2 阴性复发。尽管 Claudin18.2 靶向 CAR-T 细胞输注后抗原阴性复发，但患者仍持续缓解 8 个月，这表明 Claudin18.2 靶向 CAR-T 细胞治疗是治疗晚期 PC 的一种极其有效的治疗策略。
