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Enhanced therapeutic efficacy for glioblastoma immunotherapy with an oncolytic herpes simplex virus armed with anti-PD-1 antibody and IL-12.
- Source :
-
Molecular therapy. Oncology [Mol Ther Oncol] 2024 Apr 06; Vol. 32 (2), pp. 200799. Date of Electronic Publication: 2024 Apr 06 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Glioblastoma is the most common and aggressive malignant brain tumor and has limited treatment options. Hence, innovative approaches are urgently needed. Oncolytic virus therapy is emerging as a promising modality for cancer treatment due to its tumor-specific targeting and immune-stimulatory properties. In this study, we developed a new generation of oncolytic herpes simplex virus C5252 by deletion of a 15-kb internal repeat region and both copies of γ34.5 genes. Additionally, C5252 was armed with anti-programmed cell death protein 1 antibody and interleukin-12 to enhance its therapeutic efficacy for glioblastoma immune-virotherapy. In vitro and in vivo experiments demonstrate that C5252 has a remarkable safety profile and potent anti-tumor activity against glioblastoma. Mechanistic studies demonstrated that C5252 specifically induces cell apoptosis by caspase-3/7 activation via downregulating ciliary neurotrophic factor receptor α. Furthermore, the enhanced anti-tumor therapeutic efficacy of C5252 in a subcutaneous glioblastoma model and an orthotopic glioblastoma model was confirmed. Moreover, syngeneic mouse models showed that the murine surrogate of C5252 has superior anti-tumor activity compared to the unarmed backbone virus, with enhanced immune activation. Taken together, our findings support C5252 as a promising therapeutic option for glioblastoma treatment, positioning it as a highly promising candidate for clinical translation.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2024.)
Details
- Language :
- English
- ISSN :
- 2950-3299
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38681801
- Full Text :
- https://doi.org/10.1016/j.omton.2024.200799