ArticleMolecular therapy oncolytics2019
Deletion of Apoptosis Inhibitor F1L in Vaccinia Virus Increases Safety and Oncolysis for Cancer Therapy.
Article in Molecular therapy oncolytics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Enhanced replication and immunogenicity of a genome-modified non-replicating vaccinia virus Tiantan strain for robust low-dose protection in mice.Journal of virology · 2026Article
- Vinorelbine enhances the efficacy of oncolytic vaccinia virus in a preclinical model of ovarian high-grade serous carcinoma.Molecular therapy. Oncology · 2026Article
- Oncolytic viruses: advanced strategies in cancer therapy.Signal transduction and targeted therapy · 2026Review
- A comprehensive review redefining viruses as therapeutic agents in cancer treatment.Discover oncology · 2025Review
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- Vaccinia Virus-A Swiss Army Knife Against Cancer.Cancers · 2025Review
- Nanoengineering-armed oncolytic viruses drive antitumor response: progress and challenges.MedComm · 2024Review
- Review
- OncolyticTurkish journal of haematology : official journal of Turkish Society of Haematology · 2024Article
- Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy: a comprehensive review.Cancer biology & medicine · 2023Review
- Activation of the NLRP1 inflammasome in human keratinocytes by the dsDNA mimetic poly(dA:dT).Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Fatty acid transport protein inhibition sensitizes breast and ovarian cancers to oncolytic virus therapyFrontiers in immunology · 2023Article
- Viruses as tools in gene therapy, vaccine development, and cancer treatment.Archives of virology · 2022Review
- Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment.Journal for immunotherapy of cancer · 2022Review
- Immunogenic cell death and its therapeutic or prognostic potential in high-grade glioma.Genes and immunity · 2022Review
- Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer.Frontiers in immunology · 2022Article
- Vaccinia Virus: From Crude Smallpox Vaccines to Elaborate Viral Vector Vaccine Design.Biomedicines · 2021Review
- Immunomodulatory Arming Factors-The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules.International journal of molecular sciences · 2021Review
- Oncolytic Virus-Induced Autophagy in Glioblastoma.Cancers · 2021Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vaccinia virus (VACV) possesses a great safety record as a smallpox vaccine and has been intensively used as an oncolytic virus against various types of cancer over the past decade. Different strategies were developed to make VACV safe and selective to cancer cells. Leading clinical candidates, such as Pexa-Vec, are attenuated through deletion of the viral thymidine kinase (TK) gene, which limits virus growth to replicate in cancer tissue. However, tumors are not the only tissues whose metabolic activity can overcome the lack of viral TK. In this study, we sought to further increase the tumor-specific replication and oncolytic potential of Copenhagen strain VACV ΔTK. We show that deletion of the anti-apoptosis viral gene F1L not only increases the safety of the Copenhagen ΔTK virus but also improves its oncolytic activity in an aggressive glioblastoma model. The additional loss of F1L does not affect VACV replication capacity, yet its ability to induce cancer cell death is significantly increased. Our results also indicate that cell death induced by the Copenhagen ΔTK/F1L mutant releases more immunogenic signals, as indicated by increased levels of IL-1β production. A cytotoxicity screen in an NCI-60 panel shows that the ΔTK/F1L virus induces faster tumor cell death in different cancer types. Most importantly, we show that, compared to the TK-deleted virus, the ΔTK/F1L virus is attenuated in human normal cells and causes fewer pox lesions in murine models. Collectively, our findings describe a new oncolytic vaccinia deletion strain that improves safety and increases tumor cell killing.
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Registered trials
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