MGH Cancer Center, Massachusetts General Hospital & Harvard Medical School , Boston, MA, USA.
Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital & Harvard Medical School , Boston, MA, USA.
Expert Opin Investig Drugs. 2020 Nov;29(11):1187-1193. doi: 10.1080/13543784.2020.1826436. Epub 2020 Oct 6.
Glioblastoma (GBM) is the most common primary malignant central nervous system tumor and has a poor overall outcome despite an aggressive standard-of-care treatment. Hence, better therapeutic modalities are necessary. Immunotherapy is a novel modality that has an indirect action against the tumor cells through activation of an anti-tumor immune response.
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) belongs to a class of molecules called immune checkpoints that are inherently expressed on immune cells and lead to attenuation of the immune response. Inhibition of such molecules has been approved for the treatment of melanoma, and prolonged survival and complete responses have been reported in preclinical GBM mouse models. Ipilimumab inhibits CTLA-4 and is being investigated for the treatment of GBM, alone or in combination with other treatment modalities, in various preclinical and clinical studies, the results of the most relevant of which are discussed in this review.
Combining ipilimumab with other immunotherapy modalities and using it in specific conditions may increase the rate of objective responses in patients with GBM.
胶质母细胞瘤（GBM）是最常见的原发性恶性中枢神经系统肿瘤，尽管采用了积极的标准治疗方法，但总体预后仍较差。因此，需要更好的治疗方法。免疫疗法是一种通过激活抗肿瘤免疫反应对肿瘤细胞产生间接作用的新方法。
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）属于一类称为免疫检查点的分子，其在免疫细胞上固有表达，并导致免疫反应减弱。此类分子的抑制已被批准用于治疗黑色素瘤，并且在临床前 GBM 小鼠模型中已报道了延长的生存和完全缓解。Ipilimumab 抑制 CTLA-4，并正在各种临床前和临床研究中单独或与其他治疗方法联合用于 GBM 的治疗，本综述讨论了其中最相关的研究结果。
将 ipilimumab 与其他免疫疗法联合使用，并在特定情况下使用，可能会提高 GBM 患者的客观缓解率。
