An effective therapeutic regime for treatment of glioma using oncolytic vaccinia virus expressing IL-21 in combination with immune checkpoint inhibition

溶瘤病毒 免疫系统 胶质瘤 癌症研究 肿瘤微环境 医学 免疫疗法 病毒 免疫检查点 牛痘 免疫学 生物 重组DNA 生物化学 基因
作者
Yijie Sun,Zhe Zhang,Chenglin Zhang,Na Zhang,Pengju Wang,Yongchao Chu,Louisa S. Chard,Nicholas R. Lemoine,Yaohe Wang
出处
期刊:Molecular Therapy - Oncolytics [Elsevier BV]
卷期号:26: 105-119 被引量:5
标识
DOI:10.1016/j.omto.2022.05.008
摘要

Glioblastoma (GBM) is the most common primary malignant tumor in the brain, accounting for 51.4% of all primary brain tumors. GBM has a highly immunosuppressive tumor microenvironment (TME) and, as such, responses to immunotherapeutic strategies are poor. Vaccinia virus (VV) is an oncolytic virus that has shown tremendous therapeutic effect in various tumor types. In addition to its directly lytic effect on tumor cells, it has an ability to enhance immune cell infiltration into the TME allowing for improved immune control over the tumor. Here, we used a new generation of VV expressing the therapeutic payload interleukin-21 to treat murine GL261 glioma models. After both intratumoral and intravenous delivery, virus treatment induced remodeling of the TME to promote a robust anti-tumor immune response that resulted in control over tumor growth and long-term survival in both subcutaneous and orthotopic mouse models. Treatment efficacy was significantly improved in combination with systemic α-PD1 therapy, which is ineffective as a standalone treatment but synergizes with oncolytic VV to enhance therapeutic outcomes. Importantly, this study also revealed the upregulation of stem cell memory T cell populations after the virus treatment that exert strong and durable anti-tumor activity.
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