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

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Tác giả: Lin Fang, Jian Gao, Diancheng Hang, Jiaqi Jin, Hongmei Liu, Yang Liu, Xiaoqian Wang, Hengzhu Zhang, Xuefeng Zhang, Yufu Zhu

Ngôn ngữ: eng

Ký hiệu phân loại: 271.6 *Passionists and Redemptorists

Thông tin xuất bản: England : Experimental hematology & oncology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 148418

 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.
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