PDF(Pubmed)
Abstract：
The most common primary brain tumor is glioblastoma (GBM), yet the current therapeutic options for this disease are not promising. Although immunotherapeutic techniques have shown poor success in GBM thus far despite efforts, new developments provide optimism. One of these developments is chimeric antigen receptor (CAR)-T cell treatment, which includes removing and genetically modifying autologous T cells to produce a receptor that targets a GBM antigen before reintroducing the cells into the patient\'s body. A number of preclinical studies have produced encouraging results, which have led to the start of clinical trials assessing these CAR-T cell treatments for GBM and other brain tumors. Although results in tumors such as diffuse intrinsic pontine gliomas and lymphomas have been promising, preliminary findings in GBM have not produced any clinical benefits. The paucity of particular antigens in GBM, their inconsistent expression patterns, and the possible immunoediting-induced loss of these antigens after antigen-targeted therapy are some possible causes for this discrepancy. The goal of this systematic literature review is to assess potential approaches for creating CAR-T cells that are more effective for this indication, as well as the clinical experiences that are already being had with CAR-T cell therapy in GBM. Up until 9 May 2024, a thorough search was carried out across the three main medical databases: PubMed, Web of Science, and Scopus. Relevant Medical Subject Heading (MeSH) terms and keywords associated with \"glioblastoma\", \"CAR-T\", \"T cell therapy\", \"overall survival\", and \"progression free survival\" were employed in the search approach. Preclinical and clinical research on the application of CAR-T cells as a therapeutic approach for GBM are included in the review. A total of 838 papers were identified. Of these, 379 articles were assessed for eligibility, resulting in 8 articles meeting the inclusion criteria. The included studies were conducted between 2015 and 2023, with a total of 151 patients enrolled. The studies varied in CAR-T cell types. EGFRvIII CAR-T cells were the most frequently investigated, used in three studies (37.5%). Intravenous delivery was the most common method of delivery (62.5%). Median OS ranged from 5.5 to 11.1 months across the studies. PFS was reported in only two studies, with values of 7.5 months and 1.3 months. This systematic review highlights the evolving research on CAR-T cell therapy for GBM, emphasizing its potential despite challenges. Targeting antigens like EGFRvIII and IL13Rα2 shows promise in treating recurrent GBM. However, issues such as antigen escape, tumor heterogeneity, and immunosuppression require further optimization. Innovative delivery methods, combination therapies, and personalized approaches are crucial for enhancing CAR-T cell efficacy. Ongoing research is essential to refine these therapies and improve outcomes for GBM patients.
摘要：
最常见的原发性脑肿瘤是胶质母细胞瘤（GBM），然而，目前这种疾病的治疗方案并不乐观。尽管到目前为止，免疫治疗技术在GBM中取得了很低的成功，但尽管做出了努力，新的发展提供了乐观。这些发展之一是嵌合抗原受体（CAR）-T细胞治疗，其中包括去除和遗传修饰自体T细胞，以产生靶向GBM抗原的受体，然后再将细胞重新引入患者体内。多项临床前研究取得了令人鼓舞的成果,这导致了临床试验的开始，评估这些CAR-T细胞治疗GBM和其他脑肿瘤。虽然肿瘤如弥漫性脑桥脑胶质瘤和淋巴瘤的结果是有希望的，GBM的初步发现没有产生任何临床益处.GBM中缺乏特定的抗原，他们不一致的表达模式，抗原靶向治疗后可能的免疫编辑诱导的这些抗原的丢失是这种差异的一些可能原因。本系统文献综述的目的是评估产生对该适应症更有效的CAR-T细胞的潜在方法。以及已经在GBM中使用CAR-T细胞疗法的临床经验。直到2024年5月9日，对三个主要的医学数据库进行了彻底的搜索：PubMed，WebofScience,还有Scopus.与“胶质母细胞瘤”相关的相关医学主题标题（MeSH）术语和关键词，\"CAR-T\",“T细胞疗法”，“总生存率”，和“无进展生存期”被用于搜索方法。本文综述了CAR-T细胞作为GBM治疗方法的临床前和临床研究。共确定了838篇论文。其中,379篇文章被评估为合格，导致8篇文章符合纳入标准。纳入的研究在2015年至2023年之间进行，共有151名患者入组。这些研究在CAR-T细胞类型上有所不同。EGFRvIIICAR-T细胞是最常见的研究，用于三项研究（37.5％）。静脉分娩是最常见的分娩方式（62.5%）。在所有研究中，中位OS为5.5至11.1个月。只有两项研究报告了PFS，值为7.5个月和1.3个月。这篇系统综述强调了GBM的CAR-T细胞治疗的不断发展的研究，尽管面临挑战，但仍强调其潜力。靶向抗原如EGFRvIII和IL13Rα2在治疗复发性GBM中显示出希望。然而,抗原逃逸等问题，肿瘤异质性，和免疫抑制需要进一步优化。创新的交付方式，联合疗法,个性化方法对于增强CAR-T细胞功效至关重要。正在进行的研究对于完善这些疗法和改善GBM患者的预后至关重要。
