Nature Cancer ｜CAR-T细胞疗法为晚期肉瘤患者带来新希望
专业点燃希望约 5 分钟本研究采用的是开放标签（open label）、剂量递增（dose escalation）的I期临床试验设计。主要目的是评估HER2 CAR-T细胞在淋巴细胞清除后的安全性，次要目的是评估其抗肿瘤活性。该临床试验分为三个治疗组，研究者首先招募患者进入A组，观察安全性。如果没有出现剂量限制性毒性，则继续招募患者进入B组，使用更强的淋巴细胞清除方案。同样，如果没有出现剂量限制性毒性，则继续招募患者进入C组，输注更高剂量的CAR-T细胞。临床试验最后选取了14名符合条件的HER2过量表达肉瘤患者。
安全性
有效性
CAR-T细胞动力学
撰文
责编
制作
排版 | Sheila 校对 | uu
延伸阅读
*本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系[email protected]。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。
▼滑动查看更多▼
原文摘要（Abstract）
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 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 .
DOI:10.1038/s43018-024-00749-6