肿瘤细胞治疗研究
英文原题：Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.
Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.
在接受治疗的个体中，50% 观察到抗肿瘤活性并伴有临床获益。
在这项针对晚期肉瘤患者的前瞻性介入性 I 期研究中，研究者在氟达拉滨（Flu）和/或环磷酰胺（Cy）淋巴细胞清除后输注自体 HER2 特异性CAR-T 细胞（HER2 CAR-T）：A 组接受 Flu 后输注 1×10^8 个 T 细胞/m²，B 组接受 Flu/Cy 后输注 1×10^8 个 T 细胞/m²，C 组接受 Flu/Cy 后输注 1×10^8 个 CAR+ T 细胞/m²。主要结局为评估清淋后单次 HER2 CAR-T 输注的安全性，次要结局为抗肿瘤应答。13 名患者共入组 14 次，其中 7 人接受多次输注。21 次输注中有 19 次观察到 HER2 CAR-T 扩增。A、B 组中 12 人有 9 人发生 1–2 级细胞因子释放综合征（CRS）；C 组 2 人出现剂量限制性毒性，表现为 3–4 级 CRS。接受治疗的患者中，50% 观察到具有临床获益的抗肿瘤活性。分析的肿瘤样本显示免疫细胞存在空间异质性，并按肉瘤类型和治疗应答聚类。结果支持 HER2 作为 CAR-T 靶点，并显示该治疗用于肉瘤的安全性。ClinicalTrials.gov 注册号：NCT00902044。
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 10 8 T cells per m 2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 10 8 CAR + T cells per m 2 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 .
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