2. Academic Validation
  3. Engineered oncolytic virus coated with anti-PD-1 and alendronate for ameliorating intratumoral T cell hypofunction

Engineered oncolytic virus coated with anti-PD-1 and alendronate for ameliorating intratumoral T cell hypofunction

  • Exp Hematol Oncol. 2025 Feb 15;14(1):16. doi: 10.1186/s40164-025-00611-0.
Yufu Zhu # 1 2,  Xuefeng Zhang # 3,  Jiaqi Jin # 3 4,  Xiaoqian Wang # 3,  Yang Liu 5,  Jian Gao 3,  Diancheng Hang 3,  Lin Fang 6,  Hengzhu Zhang 7 8,  Hongmei Liu 9 10
Affiliations

Affiliations

  • 1 Institute of Nervous System Diseases, Xuzhou Medical University, No.84 Huaihai West Road, Xuzhou, 221002, China. fugle99@126.com.
  • 2 Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, 221002, China. fugle99@126.com.
  • 3 Institute of Nervous System Diseases, Xuzhou Medical University, No.84 Huaihai West Road, Xuzhou, 221002, China.
  • 4 Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, 221002, China.
  • 5 Department of Neurosurgery, The First Hospital of China Medical University, No. 155, Nanjing Bei Street, Shenyang, 110001, China.
  • 6 Cancer Institute, Xuzhou Medical University, No. 209, Tongshan Road, Xuzhou, 221004, China. fanglinzhqf@163.com.
  • 7 Institute of Nervous System Diseases, Xuzhou Medical University, No.84 Huaihai West Road, Xuzhou, 221002, China. zhanghengzhu@sina.com.
  • 8 Department of Neurosurgery, The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou University, No. 98, Nantong West Road, Yangzhou, 225009, China. zhanghengzhu@sina.com.
  • 9 Institute of Nervous System Diseases, Xuzhou Medical University, No.84 Huaihai West Road, Xuzhou, 221002, China. liuhm@sustech.edu.cn.
  • 10 Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088, Xueyuan Avenue, Shenzhen, 518055, China. liuhm@sustech.edu.cn.
  • # Contributed equally.
PMID: 39955603 DOI: 10.1186/s40164-025-00611-0
Abstract

Background: Glioblastoma is a highly aggressive and devastating primary brain tumor that is resistant to conventional therapies. Oncolytic viruses represent a promising therapeutic approach for glioblastoma by selectively lysing tumor cells and eliciting an anti-tumor immune response. However, the clinical efficacy of oncolytic viruses is often hindered by challenges such as short persistence, host Antiviral immune responses, and T cell dysfunction.

Methods: We have developed a novel therapeutic strategy by "dressing" oncolytic viruses with anti-PD-1 Antibodies and alendronate (PD-1/Al@OV) to prevent premature clearance of the oncolytic viruses and enhance T cell function, thereby improving immunotherapy outcomes against glioma.

Results: We found that in the high Reactive Oxygen Species environment of the tumor, PD-1/Al@OV disassembled to release oncolytic viruses, anti-PD-1, and alendronate. The released anti-PD-1 blocked the PD-1/PD-L1 pathway, activating T cells; the alendronate eliminated tumor-associated macrophages, increasing the concentration of oncolytic viruses; and the oncolytic viruses directly lysed Cancer cells, enhancing intratumoral T cell infiltration.

Conclusion: This approach effectively improved the immunosuppressive microenvironment of glioblastoma and achieved a robust anti-tumor effect. Consequently, this study presents a novel strategy for immune combination therapy and the improvement of the glioblastoma immune microenvironment, thereby offering new prospects for the clinical application of oncolytic viruses.

Keywords

Alendronate; Anti-PD-1; Glioblastoma; Oncolytic viruses; Tumor-associated macrophages.

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