Sperring Colin P, Argenziano Michael G, Savage William M, Teasley Damian E, Upadhyayula Pavan S, Winans Nathan J, Canoll Peter, Bruce Jeffrey N
Department of Neurological Surgery, Columbia University Irving Medical Center/NY-Presbyterian Hospital, New York, New York, USA.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY-Presbyterian Hospital, New York, New York, USA.
Neurooncol Adv. 2023 Apr 21;5(1):vdad044. doi: 10.1093/noajnl/vdad044. eCollection 2023 Jan-Dec.
The prognosis for glioblastoma has remained poor despite multimodal standard of care treatment, including temozolomide, radiation, and surgical resection. Further, the addition of immunotherapies, while promising in a number of other solid tumors, has overwhelmingly failed in the treatment of gliomas, in part due to the immunosuppressive microenvironment and poor drug penetrance to the brain. Local delivery of immunomodulatory therapies circumvents some of these challenges and has led to long-term remission in select patients. Many of these approaches utilize convection-enhanced delivery (CED) for immunological drug delivery, allowing high doses to be delivered directly to the brain parenchyma, avoiding systemic toxicity. Here, we review the literature encompassing immunotherapies delivered via CED-from preclinical model systems to clinical trials-and explore how their unique combination elicits an antitumor response by the immune system, decreases toxicity, and improves survival among select high-grade glioma patients.
尽管采用了包括替莫唑胺、放疗和手术切除在内的多模式标准治疗方案，但胶质母细胞瘤的预后仍然很差。此外，虽然免疫疗法在许多其他实体瘤中显示出前景，但在治疗胶质瘤方面却大多失败了，部分原因是免疫抑制微环境以及药物对大脑的渗透性差。局部递送免疫调节疗法规避了其中一些挑战，并使部分患者实现了长期缓解。这些方法中的许多都利用对流增强递送（CED）进行免疫药物递送，从而能够将高剂量药物直接递送至脑实质，避免全身毒性。在此，我们回顾了涵盖通过CED递送免疫疗法的文献——从临床前模型系统到临床试验——并探讨它们的独特组合如何引发免疫系统的抗肿瘤反应、降低毒性以及提高部分高级别胶质瘤患者的生存率。
