CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
从统计学视角看自体 CAR-T 细胞治疗开发中的挑战与经验教训
英文原题：Challenges and Lessons Learned in Autologous Chimeric Antigen Receptor T-Cell Therapy Development from a Statistical Perspective.
查看英文原题
Challenges and Lessons Learned in Autologous Chimeric Antigen Receptor T-Cell Therapy Development from a Statistical Perspective.
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中文摘要
嵌合抗原受体（CAR）T 细胞疗法是一种人类基因治疗产品，通过基因修饰患者 T 细胞，使其更有效识别目标抗原。近年来，自体 CAR-T 细胞显示出良好抗肿瘤活性。自 2017 年以来，美国食品药品监督管理局（FDA）已批准 6 种治疗血液系统恶性肿瘤的 CAR-T 疗法。尽管 CAR-T 疗法快速发展，其各阶段临床开发仍面临相当大的统计学挑战，亟待解决，包括剂量探索策略、估计目标（estimand）框架的实施、如何利用真实世界数据为单臂 CAR-T 试验提供背景、如何分析安全性数据，以及长期随访研究。本论文首次基于 6 种已获批 CAR-T 产品的开发经验，总结并讨论这些统计学难题。
展开英文摘要原文
Chimeric antigen receptor (CAR) T-cell therapy is a human gene therapy product where T cells from a patient are genetically modified to enable them to recognize desired target antigen(s) more effectively. In recent years, promising antitumor activity has been seen with autologous CAR T cells. Since 2017, six CAR T-cell therapies for the treatment of hematological malignancies have been approved by the Food and Drug Administration (FDA).
Despite the rapid progress of CAR T-cell therapies, considerable statistical challenges still exist for this category of products across all phases of clinical development that need to be addressed.
These include (but not limited to) dose finding strategy, implementation of the estimand framework, use of real-world data in contextualizing single-arm CAR T trials, analysis of safety data and long-term follow-up studies. This paper is the first step in summarizing and addressing these statistical hurdles based on the development of the six approved CAR T-cell products.
论文信息
- 作者
- Li D、Xu Z、Wen S、Ananthakrishnan R、Kim Y、Rantell KR、Anderson P、Whitmore J
- 单位
- Bristol Myers Squibb, Seattle, WA, USA. daniel.li1@bms.com.United States
- 期刊
- Therapeutic innovation & regulatory science2024 Sep
- 原文标识
- PubMed 38704515 · DOI 10.1007/s43441-024-00652-3