肿瘤细胞治疗研究
英文原题：Long-term control of peritoneal metastases following claudin 18.2-targeted CAR T-Cell therapy in advanced gastric cancer.
Long-term control of peritoneal metastases following claudin 18.2-targeted CAR T-Cell therapy in advanced gastric cancer.
这些发现支持 CLDN18.2 CAR-T 细胞治疗在伴腹膜转移的胃癌中具有显著且持久的活性。
伴腹膜转移的胃癌预后较差，治疗选择有限。Claudin 18.2（CLDN18.2）CAR T疗法已显示治疗晚期胃癌的活性，但其在腹膜转移疾病中的作用尚未得到充分描述。我们报告一项satri-cel I期试验（NCT03874897）中3例伴腹膜转移的胃癌患者，三者均为CLDN18.2高表达。所有患者治疗后均获得临床和影像学获益，并实现持久的腹膜疾病控制。接受CLDN18.2靶向CAR T细胞治疗后，1例患者于输注8个月后接受转化手术。随后切除双侧卵巢转移灶后，未再观察到疾病进展，腹膜转移得到长期控制。另2例患者总生存期分别为44个月和35个月。输注后约第30天，外周血循环CAR T细胞几乎检测不到，但数月后仍可在切除的胃或卵巢肿瘤组织中检测到CAR T细胞浸润。这些发现支持CLDN18.2 CAR T细胞疗法对伴腹膜转移胃癌具有显著且持久的活性。
Gastric cancer with peritoneal metastasis has a poor prognosis and limited treatment options. Claudin 18.2 (CLDN18.2) CAR T therapy has shown activity in advanced gastric cancer, but its role in peritoneal disease remains insufficiently characterized. Here, we report three patients with gastric cancer and peritoneal metastasis from a phase I trial of satri-cel (NCT03874897), all with high CLDN18.2 expression. All three patients experienced clinical and radiologic benefit after treatment and achieved durable peritoneal disease control. After CLDN18.2-targeted CAR T-cell therapy, one patient underwent conversion surgery 8 months after infusion. After resection of subsequent bilateral ovarian metastases, no further disease progression was observed, corresponding to long-term control of peritoneal metastases. The other two patients achieved overall survival of 44 and 35 months, respectively. Although circulating CAR T-cells became nearly undetectable in peripheral blood by around day 30 after infusion, CAR T-cell infiltration was still detected in resected gastric or ovarian tumor tissues months later. These findings support substantial and durable activity of CLDN18.2 CAR T-cell therapy in gastric cancer with peritoneal metastasis.
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