肿瘤细胞治疗研究
英文原题：CAR T cell therapy for glioblastoma: A review of the first decade of clinical trials.
胶质母细胞瘤（GBM）是一种侵袭性原发性脑肿瘤，预后不良，有效治疗方案很少。
胶质母细胞瘤（GBM）是一种侵袭性原发性脑肿瘤，预后差且有效治疗方案很少。研究重点已转向使用免疫疗法，如嵌合抗原受体（CAR）T细胞，以选择性靶向肿瘤抗原并在原本具有免疫抑制性的肿瘤微环境中介导细胞毒性活性。2015年至2024年间，已发表了八项已完成和两项正在进行的I期临床试验的结果。大多数研究治疗的是复发性GBM患者，尽管患者间和患者内的肿瘤异质性历来难以克服。分子靶点包括EGFR、HER2和IL13R 2，并且在改进受体构建体、识别新靶点以及添加佐剂增强剂以提高疗效方面持续取得进展。CAR T细胞已通过外周和局部区域途径安全给药，但临床和影像学疗效不一。大多数试验使用自体T细胞产品以避免免疫排斥，但未能一致地显示患者体内稳健的植入和持久性。尽管如此，诸如CAR T细胞疗法等靶向免疫疗法仍然是GBM治疗的下一个前沿领域，这一事业的普及性和复杂性在临床试验的过去、现在和未来格局中显而易见。
Glioblastoma (GBM) is an aggressive primary brain tumor with a poor prognosis and few effective treatment options. Focus has shifted toward using immunotherapies, such as chimeric antigen receptor (CAR) T cells, to selectively target tumor antigens and mediate cytotoxic activity within an otherwise immunosuppressive tumor microenvironment. Between 2015 and 2024, the results of eight completed and two ongoing phase I clinical trials have been published. The majority of studies have treated recurrent GBM patients, although the inter- and intra-patient tumor heterogeneity has been historically challenging to overcome. Molecular targets have included EGFR, HER2, and IL13R 2 and there has been continued development in improving receptor constructs, identifying novel targets, and adding adjuvant enhancers to increase efficacy. CAR T cells have been safely administered through both peripheral and locoregional routes but with variable clinical and radiographic efficacy. Most trials utilized autologous T cell products to avoid immune rejection yet were unable to consistently show robust engraftment and persistence within patients. Nonetheless, targeted immunotherapies such as CAR T cell therapy remain the next frontier for GBM treatment, and the popularity and complexity of this undertaking is evident in the past, present, and future landscape of clinical trials.
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