针对中枢神经系统恶性肿瘤患者的 CAR-T 细胞开发
The development of CAR T cells for patients with CNS malignancies.
在过去十年中,嵌合抗原受体(CAR)T细胞已成为某些复发和/或难治性血液系统恶性肿瘤患者的标准治疗手段。
英文原题:Cellular Therapy for Children with Central Nervous System Tumors: Mining and Mapping the Correlative Data.
我们强调了长期以来以及最近才被理解的挑战,这些挑战涉及有效整合相关性数据,并为当前和未来对系列肿瘤、血清和脑脊液(CSF)生物标本进行多组学分析的方法提供了实际考虑。我们强调了在ACT临床试验中从CNS肿瘤患者收集系列细胞因子和蛋白质组学的初步成功。
相关研究应利用临床试验框架进行生物样本分析,以深入了解干预措施的生物活性,并促进未来试验的迭代,从而进一步改善患者预后。在儿童细胞免疫治疗试验中,相关研究能够更深入地理解T细胞动员、免疫激活的持久性、毒性模式以及治疗反应的早期检测。在此,我们综述了针对儿童中枢神经系统(CNS)肿瘤的过继细胞治疗(ACT)中的相关科学,重点关注现有的嵌合抗原受体(CAR)和表达T细胞受体(TCR)的T细胞疗法。
我们强调了长期以来以及最近才被理解的挑战,这些挑战涉及有效整合相关性数据,并为当前和未来对系列肿瘤、血清和脑脊液(CSF)生物标本进行多组学分析的方法提供了实际考虑。我们强调了在ACT临床试验中从CNS肿瘤患者收集系列细胞因子和蛋白质组学的初步成功。
PURPOSE OF REVIEW: Correlative studies should leverage clinical trial frameworks to conduct biospecimen analyses that provide insight into the bioactivity of the intervention and facilitate iteration toward future trials that further improve patient outcomes. In pediatric cellular immunotherapy trials, correlative studies enable deeper understanding of T cell mobilization, durability of immune activation, patterns of toxicity, and early detection of treatment response. Here, we review the correlative science in adoptive cell therapy (ACT) for childhood central nervous system (CNS) tumors, with a focus on existing chimeric antigen receptor (CAR) and T cell receptor (TCR)-expressing T cell therapies. RECENT FINDINGS: We highlight long-standing and more recently understood challenges for effective alignment of correlative data and offer practical considerations for current and future approaches to multi-omic analysis of serial tumor, serum, and cerebrospinal fluid (CSF) biospecimens. We highlight the preliminary success in collecting serial cytokine and proteomics from patients with CNS tumors on ACT clinical trials.
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