颅内肿瘤由于其生理位置而提出了重大的治疗挑战。由于相对较低的毒性和肿瘤特异性，免疫疗法为靶向这些颅内肿瘤提供了一种有吸引力的方法。在这里，我们表明 SCIB1（一种 TRP-2 和 gp100 定向的ImmunoBody® DNA 疫苗）可产生强烈的 TRP-2 特异性免疫反应，如产生大量 TRP2 特异性 IFNγ 斑点和检测到大量五聚体所证明的那样。接种疫苗的小鼠脾脏中 T 细胞呈阳性。此外，经过短暂的体外培养，疫苗诱导的 T 细胞能够识别并杀死 B16HHDII/DR1 细胞。发现多形性胶质母细胞瘤 (GBM) 表达显着水平的 PD-L1 和 IDO1，而 PD-L1 与 GBM 间充质亚型患者的较差生存率相关，因此我们决定将 SCIB1 Nutrition® 与 PD-1 免疫检查点阻断相结合，以治疗患有表达 TRP-2 和 gp100 的颅内肿瘤的小鼠。死亡时间显着延长，这与组织微环境 (TME) 中 CD4 和 CD8 T 细胞浸润增加相关。然而，除了 PD-L1 和 IDO 之外，GBM TME 还被发现含有大量免疫调节 T (Treg) 细胞相关转录本，除非也得到解决，否则此类细胞的存在可能会显着影响临床结果。© 2024。作者。

Intracranial tumors present a significant therapeutic challenge due to their physiological location. Immunotherapy presents an attractive method for targeting these intracranial tumors due to relatively low toxicity and tumor specificity. Here we show that SCIB1, a TRP-2 and gp100 directed ImmunoBody® DNA vaccine, generates a strong TRP-2 specific immune response, as demonstrated by the high number of TRP2-specific IFNγ spots produced and the detection of a significant number of pentamer positive T cells in the spleen of vaccinated mice. Furthermore, vaccine-induced T cells were able to recognize and kill B16HHDII/DR1 cells after a short in vitro culture. Having found that glioblastoma multiforme (GBM) expresses significant levels of PD-L1 and IDO1, with PD-L1 correlating with poorer survival in patients with the mesenchymal subtype of GBM, we decided to combine SCIB1 ImmunoBody® with PD-1 immune checkpoint blockade to treat mice harboring intracranial tumors expressing TRP-2 and gp100. Time-to-death was significantly prolonged, and this correlated with increased CD4+ and CD8+ T cell infiltration in the tissue microenvironment (TME). However, in addition to PD-L1 and IDO, the GBM TME was found to contain a significant number of immunoregulatory T (Treg) cell-associated transcripts, and the presence of such cells is likely to significantly affect clinical outcome unless also tackled.© 2024. The Author(s).