肿瘤细胞治疗研究
英文原题：CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer.
在病例 1 中，CLDN 18.2 表达为 2+、70%，在淋巴细胞清除后输注了 250×10⁶ 个细胞。
胰腺癌缺乏有效治疗方法。本文报告 2 例转移性胰腺癌患者在标准治疗失败后接受 Claudin 18.2（CLDN18.2）CAR-T 治疗（NCT04581473 和 NCT03874897）。病例 1 的 CLDN18.2 表达为 2+、70%；患者接受淋巴细胞清除治疗后输注 250 × 10⁶ 个细胞。第 1 天出现 1 级细胞因子释放综合征（CRS），随后使用 tocilizumab 控制。按 RECIST v1.1 评估达到部分缓解（PR），肺转移灶明显缩小。患者 CD8⁺ T 细胞和 Treg 细胞增加，而 CD4⁺ T 细胞和 B 细胞减少。病例 2 的 CLDN18.2 免疫组化结果为 3+、60%，随后接受 250 × 10⁶ 个 CLDN18.2 CAR-T 细胞。患者发生 2 级 CRS，使用 tocilizumab 控制。肺转移靶病灶进一步达到完全缓解。外周血中同样检测到 CD8⁺ T 细胞和 Treg 细胞增加；同时观察到 IL-8 升高、TGF-β1 下降。截至最近一次随访（2023 年 7 月 18 日），患者肿瘤仍得到良好控制。
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 10 6 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 10 6 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- 1 were also observed. The tumor is still under well control until the last follow-up on July 18, 2023.
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