Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
ADC Biomedical Research Institute, Saint Paul, MN.
Int J Cancer. 2019 Jun 1;144(11):2867-2879. doi: 10.1002/ijc.32008. Epub 2019 Jan 7.
Owing to the limited therapeutic efficacy of glioma vaccines, new strategies are required to improve cancer vaccines. Our study aimed to assess the therapeutic efficacy of a glioma vaccine called STDENVANT. This vaccine, comprising glioma stem-like cell (GSC) lysate, dendritic cells (DCs), and Toll-like receptor (TLR) 9 agonist CpG motif-containing oligodeoxynucleotides (CpG ODNs), was assessed using a GL261-C57BL/6 orthotopic mouse model of glioma. STDENVANT markedly improved survival and tumor regression by enhancing anti-tumor immune function. Moreover, STDENVANT upregulated programmed death 1 (PD-1) and its ligand PD-L1 on effector T cells, DCs, and glioma tissues, resulting in the accumulation of regulatory T (Treg) cells in the brain and lymph nodes. Combinatorial administration of anti-PD-L1 antibody and STDENVANT conferred a greater survival advantage and decreased the Treg cell population in the brain. The present results indicate that PD-L1 blockade can promote tumor regression via STDENVANT in a mouse model of glioma, and combinatorial administration of anti-PD-L1 antibody and STDENVANT increases the therapeutic anti-tumor efficacy of treatment.
由于神经胶质瘤疫苗的治疗效果有限，需要新的策略来改进癌症疫苗。我们的研究旨在评估一种名为 STDENVANT 的神经胶质瘤疫苗的治疗效果。该疫苗由神经胶质瘤干细胞 (GSC) 裂解物、树突状细胞 (DC) 和 Toll 样受体 (TLR) 9 激动剂 CpG 基序寡脱氧核苷酸 (CpG ODN) 组成，使用 GL261-C57BL/6 原位神经胶质瘤小鼠模型进行了评估。STDEVANT 通过增强抗肿瘤免疫功能，显著提高了存活率并促进肿瘤消退。此外，STDEVANT 上调效应 T 细胞、DC 和神经胶质瘤组织上的程序性死亡 1 (PD-1)及其配体 PD-L1，导致脑和淋巴结中调节性 T (Treg)细胞的积累。抗 PD-L1 抗体和 STDENVANT 的联合给药可提供更大的生存优势，并减少脑内 Treg 细胞的数量。这些结果表明，PD-L1 阻断可通过 STDENVANT 在神经胶质瘤小鼠模型中促进肿瘤消退，联合使用抗 PD-L1 抗体和 STDENVANT 可提高治疗的抗肿瘤疗效。
