决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology.
我们的研究表明,靶向治疗的潜在疗效目前尚未在复发性胶质母细胞瘤患者的基因组驱动试验中得到体现。
对于胶质母细胞瘤患者,迄今为止靶向治疗的疗效有限。此前研究的大多数分子治疗在该人群中缺乏疗效。需要更多试验来研究生物标志物在(复发性)胶质母细胞瘤中的实际可操作性。本研究旨在评估当前的临床试验格局,以评估分子生物标志物在复发性胶质母细胞瘤治疗试验中的作用。使用ClinicalTrials.gov数据库识别尚未完成的成人复发性胶质母细胞瘤临床试验。对正在招募的研究进行评估,以调查分子标准的应用情况,并尽可能详细地提取相关信息。主要结局是作为研究参与选择标准的分子标准。此外,还收集了检测时机和方法、所研究的靶点和药物的详细信息。在纳入的研究中,76%(181/237)的研究设计未包含分子标准。在其余56项研究中,33项(59%)要求至少一种特定基因组改变作为研究参与的选择标准。EGFR、CDKN2A/B或C、CDK4/6和RB的改变最常被研究,相应的药物abemaciclib和ribociclib也是如此。在免疫治疗中,CAR-T疗法是研究最频繁的治疗方式。此前,基因组学研究已揭示胶质母细胞瘤中存在潜在可干预的改变。我们的研究表明,靶向治疗的潜在疗效目前尚未转化为复发性胶质母细胞瘤患者的基因组驱动试验。加强基因组驱动试验可能有助于为靶向治疗的(无)疗效提供证据。
For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.
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