Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, M/S JMB-8, 1900 9thAvenue, Seattle, WA, 98101, USA.
Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
Curr Oncol Rep. 2023 Aug;25(8):847-855. doi: 10.1007/s11912-023-01423-3. Epub 2023 May 9.
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.
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.
相关性研究应利用临床试验框架进行生物样本分析,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的结局。在儿科细胞免疫治疗试验中,相关性研究能够更好地了解 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。在这里,我们综述了用于儿童中枢神经系统(CNS)肿瘤的过继性细胞治疗(ACT)中的相关性科学,重点介绍了现有的嵌合抗原受体(CAR)和 T 细胞受体(TCR)表达 T 细胞疗法。
我们强调了为使相关性数据有效一致而长期存在的和最近才理解的挑战,并为当前和未来对肿瘤、血清和脑脊液(CSF)生物样本进行多组学分析的方法提供了实用的考虑因素。我们还强调了在 ACT 临床试验中从 CNS 肿瘤患者收集连续细胞因子和蛋白质组学数据的初步成功。