Warren Alpert Medical School, Brown University, Providence, RI, 02903, USA.
Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Mol Diagn Ther. 2023 Nov;27(6):643-660. doi: 10.1007/s40291-023-00671-0. Epub 2023 Sep 12.
Chimeric antigen receptor T-cell therapies have transformed the management of hematologic malignancies but have not yet demonstrated consistent efficacy in solid tumors. Glioblastoma is the most common primary malignant brain tumor in adults and remains a major unmet medical need. Attempts at harnessing the potential of chimeric antigen receptor T-cell therapy for glioblastoma have resulted in glimpses of promise but have been met with substantial challenges. In this focused review, we discuss current and future strategies being developed to optimize chimeric antigen receptor T cells for efficacy in patients with glioblastoma, including the identification and characterization of new target antigens, reversal of T-cell dysfunction with novel chimeric antigen receptor constructs, regulatable platforms, and gene knockout strategies, and the use of combination therapies to overcome the immune-hostile microenvironment.
嵌合抗原受体 T 细胞疗法已经改变了血液系统恶性肿瘤的治疗模式，但在实体肿瘤中的疗效仍不明确。胶质母细胞瘤是成人中最常见的原发性恶性脑肿瘤，仍然是一个重大的未满足的医疗需求。利用嵌合抗原受体 T 细胞疗法治疗胶质母细胞瘤的尝试已经取得了一些有希望的结果，但也面临着巨大的挑战。在这篇重点综述中，我们讨论了目前和未来正在开发的策略，以优化嵌合抗原受体 T 细胞在胶质母细胞瘤患者中的疗效，包括鉴定和表征新的靶抗原、使用新型嵌合抗原受体构建物逆转 T 细胞功能障碍、调控平台和基因敲除策略，以及使用联合疗法来克服免疫抑制性微环境。
