Department of Early Drug Development Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
J Hematol Oncol. 2023 Sep 9;16(1):102. doi: 10.1186/s13045-023-01491-9.
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 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 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.
胰腺癌缺乏有效的治疗方法。在这里，我们报告了两例转移性胰腺癌患者在标准治疗失败后接受 Claudin 18.2（CLDN 18.2）嵌合抗原受体 T 细胞（CART）治疗的情况（NCT04581473 和 NCT03874897）。在病例 1 中，CLDN 18.2 表达为 2+，在淋巴耗竭后输注了 70%、250×10 个细胞。第 1 天发生 1 级细胞因子释放综合征（CRS），随后用托珠单抗控制。根据 RECIST v1.1 标准，达到部分缓解（PR），肺转移灶明显缩小。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 的免疫组化结果显示为 3+，60%。随后给予 250×10 个 CLDN18.2 CART 细胞。患者发生 2 级 CRS，用托珠单抗控制。肺转移的靶病灶进一步达到完全缓解。从外周血中也检测到类似的 CD8+T 细胞和 Treg 细胞增加。还观察到 IL-8 升高和 TGF-β1 下降。截至 2023 年 7 月 18 日最后一次随访时，肿瘤仍得到良好控制。
