摘要
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. @@@ What's new? Vaccines based on dendritic cells harbouring glioma stem-like cell (GSC)-associated antigens are a promising therapeutic avenue against glioma, but efficacy remains limited. Here, the authors assessed the efficacy of a novel glioma vaccine called STDENVANT containing GSC lysate, dendritic cells, and CpG adjuvant. STDENVANT improved survival and tumor regression by enhancing anti-tumor immune function in an orthotopic mouse model of glioma. Moreover, addition of anti-PD-L1 mAb enhanced the therapeutic potency of the vaccine and deterred Treg cell accumulation in the tumor microenvironment. The findings revealed the potential clinical efficacy of combinatorial administration of the GSC-based vaccine with PD-L1 blocking therapy.
- 出版日期2019-6-1
- 单位吉林大学