Calinescu Anda-Alexandra, Kamran Neha, Baker Gregory, Mineharu Yohei, Lowenstein Pedro Ricardo, Castro Maria Graciela
Department of Neurosurgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Department of Neurosurgery, Kyoto University, Kyoto, Japan.
Immunotherapy. 2015;7(10):1073-104. doi: 10.2217/imt.15.75.
In the last decade, numerous studies of immunotherapy for malignant glioma (glioblastoma multiforme) have brought new knowledge and new hope for improving the prognosis of this incurable disease. Some clinical trials have reached Phase III, following positive outcomes in Phase I and II, with respect to safety and immunological end points. Results are encouraging especially when considering the promise of sustained efficacy by inducing antitumor immunological memory. Progress in understanding the mechanisms of tumor-induced immune suppression led to the development of drugs targeting immunosuppressive checkpoints, which are used in active clinical trials for glioblastoma multiforme. Insights related to the heterogeneity of the disease bring new challenges for the management of glioma and underscore a likely cause of therapeutic failure. An emerging therapeutic strategy is represented by a combinatorial, personalized approach, including the standard of care: surgery, radiation, chemotherapy with added active immunotherapy and multiagent targeting of immunosuppressive checkpoints.
在过去十年中,针对恶性胶质瘤(多形性胶质母细胞瘤)的免疫疗法的大量研究为改善这种不治之症的预后带来了新知识和新希望。一些临床试验在I期和II期取得了关于安全性和免疫终点的阳性结果后,已进入III期。尤其是考虑到诱导抗肿瘤免疫记忆所带来的持续疗效的前景,结果令人鼓舞。在理解肿瘤诱导的免疫抑制机制方面的进展导致了靶向免疫抑制检查点的药物的开发,这些药物正在用于多形性胶质母细胞瘤的积极临床试验中。与该疾病异质性相关的见解给胶质瘤的管理带来了新挑战,并突出了治疗失败的一个可能原因。一种新兴的治疗策略是以组合式、个性化方法为代表,包括护理标准:手术、放疗、添加主动免疫疗法的化疗以及对免疫抑制检查点的多靶点治疗。