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一种有效的基于树突状细胞的疫苗,包含神经胶质瘤干细胞裂解物和 CpG 佐剂,用于神经胶质瘤的原位小鼠模型。

An effective dendritic cell-based vaccine containing glioma stem-like cell lysate and CpG adjuvant for an orthotopic mouse model of glioma.

机构信息

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

ADC Biomedical Research Institute, Saint Paul, MN.

出版信息

Int J Cancer. 2019 Jun 1;144(11):2867-2879. doi: 10.1002/ijc.32008. Epub 2019 Jan 7.

Abstract

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.

摘要

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。

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