Pancreatic cancer lacks effective therapy. Here, we reported two metastatic pancreatic cancer patients administrated with Claudin 18.2 (CLDN 18.2) CART therapy after the failure of standard therapy (NCT04581473 and NCT03874897). In case 1, with CLDN 18.2 expression of 2+, 70%, 250 × 106 cells were infused after lymphodepletion. Grade 1 cytokine release syndrome (CRS) occurred on d1 which was later controlled by tocilizumab. Partial response (PR) was achieved according to RECIST v1.1, with great shrinkage of lung metastasis. An increasing CD8+ T cell and Treg cells and declining CD4+ T cell and B cell were observed. In case 2, IHC result of ClDN18.2 showed 3+, 60%. 250 × 106 CLDN18.2 CART cells were subsequently administered. Patient experienced grade 2 CRS, which was controlled with tocilizumab. Target lesions of lung metastasis further achieved complete response. Similar increasing CD8+ T cell and Treg cell was detected from peripheral blood. Elevating IL-8 and declining TGF-β1 were also observed. The tumor is still under well control until the last follow-up on July 18, 2023.

中文翻译：

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CT041 CAR T细胞疗法治疗Claudin18.2阳性转移性胰腺癌

胰腺癌缺乏有效的治疗方法。在这里，我们报告了两名转移性胰腺癌患者在标准治疗失败后接受 Claudin 18.2 (CLDN 18.2) CART 治疗（NCT04581473 和 NCT03874897）。在病例 1 中，CLDN 18.2 表达为 2+，70%，淋巴细胞清除后输注 250 × 106 个细胞。第 1 天发生 1 级细胞因子释放综合征 (CRS)，随后通过托珠单抗控制。根据RECIST v1.1达到部分缓解（PR），肺转移大幅缩小。观察到 CD8+ T 细胞和 Treg 细胞增加，CD4+ T 细胞和 B 细胞减少。在病例2中，ClDN18.2的IHC结果显示3+，60%。随后施用 250 × 106 CLDN18.2 CART 细胞。患者出现 2 级 CRS，并用托珠单抗控制。肺转移靶病灶进一步实现完全缓解。从外周血中检测到类似增加的CD8+T细胞和Treg细胞。还观察到 IL-8 升高和 TGF-β1 下降。直至2023年7月18日最后一次随访，肿瘤仍得到良好控制。