原发性脑肿瘤免疫治疗和疫苗策略的研究进展

icartab

An Update on the Role of Immunotherapy and Vaccine Strategies for Primary Brain Tumors.

Abstract

Existing therapies for glioblastoma (GBM), the most common malignant primary brain tumor in adults, have fallen short of improving the dismal patient outcomes, with an average 14-16-month median overall survival. The biological complexity and adaptability of GBM, redundancy of dysregulated signaling pathways, and poor penetration of therapies through the blood-brain barrier contribute to poor therapeutic progress. The current standard of care for newly diagnosed GBM consists of maximal safe resection, followed by fractionated radiotherapy combined with concurrent temozolomide (TMZ) and 6-12 cycles of adjuvant TMZ. At progression, bevacizumab with or without additional chemotherapy is an option for salvage therapy. The recent FDA approval of sipuleucel-T for prostate cancer and ipilumimab, nivolumab, and pembrolizumab for select solid tumors and the ongoing trials showing clinical efficacy and response durability herald a new era of cancer treatment with the potential to change standard-of-care treatment across multiple cancers. The evaluation of various immunotherapeutics is advancing for GBM, putting into question the dogma of the CNS as an immuno-privileged site. While the field is yet young, both active immunotherapy involving vaccine strategies and cellular therapy as well as reversal of GBM-induced global immune-suppression through immune checkpoint blockade are showing promising results and revealing essential immunological insights regarding kinetics of the immune response, immune evasion, and correlative biomarkers. The future holds exciting promise in establishing new treatment options for GBM that harness the patients' own immune system by activating it with immune checkpoint inhibitors, providing specificity using vaccine therapy, and allowing for modulation and enhancement by combinatorial approaches.

KEYWORDS:

Autologous T cells; CAR T cells; Checkpoint blockade; EGFRvIII; GBM; Immunotherapy; Rindopepimut; Vaccines

原发性脑肿瘤免疫治疗和疫苗策略的研究进展。

摘要

胶质母细胞瘤（GBM）是一种成年人中最常见的原发性恶性脑肿瘤。目前的治疗方案，没有太好的治疗方式改善患者治疗结果，平均中位生期为14-16个月。GBM的生物复杂性，过多的信号途径失调以及血脑屏障的低渗透性导致了该疾病治疗的进展缓慢。目前标准的治疗新诊断的GBM包括安全的最大程度的切除病灶，接下来是分次放疗同步使用替莫唑胺（TMZ）和6-12周期TMZ辅助。在研究进展中，使用或者不适用贝伐单抗辅助化疗是抢救治疗GBM的选择。最近，FDA批准sipuleucel-T治疗前列腺癌，ipilumimab、nivolumab和pembrolizumab选择性用于实体肿瘤，进展中的临床试验显示了临床有效性。这说明了癌症治疗进入了一个新的纪元，并且有潜力改变多种癌症的治疗标准。把中枢神经系统作为一种免疫特殊的区域，评估各种免疫治疗方案来推动GBM。然而这个领域的研究时间还很短，涉及到疫苗和细胞治疗的主动免疫策略，通过免疫检查点抑制逆转GBM导致的全部免疫抑制，这些治疗方案都显示了有希望的结果，并且揭示了免疫反应动力学、免疫逃避和相关的生物标记物的基本见解。将来通过免疫检查点抑制，通过使用特异性的免疫疫苗，激发利用患者自身的免疫系统。利用组合治疗的方式调节或增强，将来将给GBM的治疗带来希望。

关键词：

Autologous T cells; CAR T cells; Checkpoint blockade; EGFRvIII; GBM; Immunotherapy; Rindopepimut; Vaccines

自体T细胞，T细胞；汽车；检查点阻断；EGFRvIII；GBM；免疫治疗；rindopepimut；疫苗

出自爱康得生物技术