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一期试验

原文发布日期：2024-04-24

英文摘要：

摘要翻译：

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一期试验

a phase 1 trial

原文发布日期：2024-04-24

英文摘要：

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1–2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3–4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044.

摘要翻译：

在本项针对晚期乳腺癌患者的研究中，我们采用了干预性Ⅰ期研究的方法，在完成淋巴结清除（采用氟尿嘧啶±顺式嘌呤醇）后，将自体HER2特异性融合抗原受体T细胞（HER2 CAR T细胞）注入患者体内。具体做法是在接受治疗的患者身上分别注射1×10^8 CAR+ T细胞每平方米：在 cohort A 中，为接受氟尿嘧啶单药治疗的患者注入1×10^8 T细胞每平方米；在 cohort B 中，则在接受氟尿嘧啶联合顺式嘌呤醇治疗后，为患者注入1×10^8 CAR+ T细胞每平方米。研究的主要目的是评估HER2 CAR T细胞在淋巴结清除后安全性的单一给药剂量。抗肿瘤反应的确定是次要结果。共招募了14名受试者，其中7人接受多次输注治疗。HER2 CAR T细胞在21次输注中部分实现了扩增。 cohorts A 和 B 中的11名受试者出现了I-Ⅱ期细胞因子释放综合征。cohort C 中的2名受试者出现了3-4级细胞因子释放综合征，剂量限值毒性。50%接受治疗的受试者显示出临床反应。肿瘤标本分析显示，免疫细胞的空间异质性以及肿瘤类型和治疗反应的聚类特征均存在。这些结果证实了HER2作为CAR T细胞靶点的可能性，并表明该治疗方法在乳腺癌中的安全性。