1. Enhancing antitumor efficacy of oncolytic virus M1 via albendazole-sustained CD8+ T cell activation
- Author
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Wenjing Bai, Xia Tang, Tong Xiao, Yangyang Qiao, Xuyan Tian, Bo Zhu, Jiehong Chen, Chaoxin Chen, Yuanyuan Li, Xueying Lin, Jing Cai, Yuan Lin, Wenbo Zhu, Guangmei Yan, Jiankai Liang, and Jun Hu
- Subjects
oncolytic virus ,albendazole ,CD8+T ,anti-tumor ,CTLA4 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The immune response plays a crucial role in the functionality of oncolytic viruses. In this study, Albendazole, an antihelminthic drug known to modulate the immune checkpoint PD-L1, was combined with the oncolytic virus M1 (OVM1) to treat mice with either prostate cancer (RM-1) or glioma (GL261) tumors. This combination therapy enhanced anti-tumor effects in immunocompetent mice, but not in immunodeficient ones, without increasing OVM1 replication. Instead, it led to an increase in the number of CD8+ T cells within the tumor, downregulated the expression of PD1 on CD8+ T cells, and upregulated activation markers such as Ki67, CD44, and CD69 and the secretion of cytotoxic factors including interferon (IFN)-γ, granzyme B, and tumor necrosis factor (TNF)-α. Consistently, it enhanced the in vitro tumor-killing activity of lymphocytes from tumor-draining lymph nodes or spleens. The synergistic effect of Albendazole on OVM1 was abolished by depleting CD8+ T cells, suggesting a CD8+ T cell-dependent mechanism. In addition, Albendazole and OVM1 therapy increased CTLA4 expression in the spleen, and the addition of CTLA4 antibodies further enhanced the anti-tumor efficacy in vivo. In summary, Albendazole can act synergistically with oncolytic viruses via CD8+ T cell activation, and the Albendazole/OVM1 combination can overcome resistance to CTLA4-based immune checkpoint blockade therapy.
- Published
- 2024
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