Lechpammer Mirna, Rao Rohan, Shah Sanjit, Mirheydari Mona, Bhattacharya Debanjan, Koehler Abigail, Toukam Donatien Kamdem, Haworth Kevin J, Pomeranz Krummel Daniel, Sengupta Soma
Foundation Medicine, Inc., Cambridge, MA 02141, USA.
Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Cancers (Basel). 2022 Mar 23;14(7):1627. doi: 10.3390/cancers14071627.
Glioblastoma, or glioblastoma multiforme (GBM, WHO Grade IV), is a highly aggressive adult glioma. Despite extensive efforts to improve treatment, the current standard-of-care (SOC) regimen, which consists of maximal resection, radiotherapy, and temozolomide (TMZ), achieves only a 12-15 month survival. The clinical improvements achieved through immunotherapy in several extracranial solid tumors, including non-small-cell lung cancer, melanoma, and non-Hodgkin lymphoma, inspired investigations to pursue various immunotherapeutic interventions in adult glioblastoma patients. Despite some encouraging reports from preclinical and early-stage clinical trials, none of the tested agents have been convincing in Phase III clinical trials. One, but not the only, factor that is accountable for the slow progress is the blood-brain barrier, which prevents most antitumor drugs from reaching the target in appreciable amounts. Herein, we review the current state of immunotherapy in glioblastoma and discuss the significant challenges that prevent advancement. We also provide thoughts on steps that may be taken to remediate these challenges, including the application of ultrasound technologies.
胶质母细胞瘤，即多形性胶质母细胞瘤（GBM，世界卫生组织IV级），是一种侵袭性很强的成人胶质瘤。尽管为改善治疗付出了巨大努力，但目前的标准治疗（SOC）方案，包括最大限度切除、放疗和替莫唑胺（TMZ），仅能实现12至15个月的生存期。免疫疗法在包括非小细胞肺癌、黑色素瘤和非霍奇金淋巴瘤在内的几种颅外实体瘤中取得的临床改善，激发了对成人胶质母细胞瘤患者进行各种免疫治疗干预的研究。尽管临床前和早期临床试验有一些令人鼓舞的报告，但在III期临床试验中，没有一种受试药物令人信服。导致进展缓慢的一个（但不是唯一的）因素是血脑屏障，它阻止大多数抗肿瘤药物以可观的量到达靶点。在此，我们综述了胶质母细胞瘤免疫治疗的现状，并讨论了阻碍其进展的重大挑战。我们还就可能采取的应对这些挑战的措施提出了想法，包括超声技术的应用。
