Department of Neurological Surgery, University of California, Diller Family Cancer Research Building HD 472, Box 520, 1450 3rd Street San Francisco, Helen, CA, 94158, USA.
Department of Neurology, University of California, San Francisco, CA, USA.
Curr Oncol Rep. 2021 Jan 26;23(2):21. doi: 10.1007/s11912-020-01007-5.
This review seeks to inform oncology clinicians and researchers about the development of novel immunotherapies for the treatment of glioblastoma. An enumeration of ongoing and recently completed clinical trials will be discussed with special attention given to current technologies implemented to overcome central nervous system-specific challenges including barriers to the peripheral immune system, impaired antigen presentation, and T cell dysfunction.
The success of immunotherapy in other solid cancers has served as a catalyst to explore its application in glioblastoma, which has limited response to other treatments. Recent developments include multi-antigen vaccines that seek to overcome the heterogeneity of glioblastoma, as well as immune checkpoint inhibitors, which could amplify the adaptive immune response and may have promise in combinatorial approaches. Additionally, oncolytic and retroviruses have opened the door to a plethora of combinatorial approaches aiming to leverage their immunogenicity and/or ability to carry therapeutic transgenes. Treatment of glioblastoma remains a serious challenge both with regard to immune-based as well as other therapeutic strategies. The disease has proven to be highly resistant to treatment due to a combination of tumor heterogeneity, adaptive expansion of resistant cellular subclones, evasion of immune surveillance, and manipulation of various signaling pathways involved in tumor progression and immune response. Immunotherapeutics that are efficacious in other cancer types have unfortunately not enjoyed the same success in glioblastoma, illustrating the challenging and complex nature of this disease and demonstrating the need for development of multimodal treatment regimens utilizing the synergistic qualities of immune-mediated therapies.
本综述旨在为肿瘤临床医生和研究人员提供关于新型免疫疗法治疗胶质母细胞瘤的信息。本文将讨论正在进行和最近完成的临床试验，并特别关注为克服中枢神经系统特有的挑战而采用的当前技术，包括外周免疫系统的障碍、抗原呈递受损和 T 细胞功能障碍。
免疫疗法在其他实体瘤中的成功应用为探索其在胶质母细胞瘤中的应用提供了契机，后者对其他治疗方法的反应有限。最近的进展包括旨在克服胶质母细胞瘤异质性的多抗原疫苗，以及免疫检查点抑制剂，这些抑制剂可以增强适应性免疫反应，并可能在联合治疗中具有潜力。此外，溶瘤病毒和逆转录病毒为多种组合方法打开了大门，旨在利用其免疫原性和/或携带治疗性转基因的能力。胶质母细胞瘤的治疗仍然是一个严重的挑战，无论是免疫治疗还是其他治疗策略。由于肿瘤异质性、耐药细胞亚克隆的适应性扩张、免疫逃避以及涉及肿瘤进展和免疫反应的各种信号通路的操纵，该疾病已被证明对治疗具有高度耐药性。在其他癌症类型中有效的免疫疗法在胶质母细胞瘤中并没有取得同样的成功，这说明了这种疾病具有挑战性和复杂性，并表明需要开发利用免疫介导疗法的协同特性的多模式治疗方案。
