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DC Field | Value | Language |
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dc.contributor.advisor | Mossman, Karen | - |
dc.contributor.author | Baracuhy, Enzo Mongiovi | - |
dc.date.accessioned | 2024-05-29T16:58:32Z | - |
dc.date.available | 2024-05-29T16:58:32Z | - |
dc.date.issued | 2024 | - |
dc.identifier.uri | http://hdl.handle.net/11375/29821 | - |
dc.description.abstract | Viral immunotherapy is a promising approach for cancer treatment where viruses can selectively target and kill cancer cells while also stimulating an immune response. Among viruses with this ability, Bovine herpesvirus type-1 (BHV-1) has several advantages, including previous data suggesting it does not require viral replication for its anti-cancer effects. We have previously demonstrated that binding and penetration of enveloped virus particles are sufficient to trigger intrinsic and innate immune signalling. In addition, we have published data showing mutated herpesviruses with lower replication in vitro exhibit stronger anti-tumour activity in vivo. Experiments in established animal models comparing the survival of mice bearing melanoma C10 cells treated with either live or UV (non-replicating) BHV-1 show that both viruses similarly extend survival. Transcriptomic analysis of C10 cells and tumours treated with either live or UV-inactivated BHV-1 has revealed a subset of overlapping differentially regulated genes and similar pathway enrichments, suggesting live and UV BHV-1 have similar mechanisms of activity. Lastly, the infiltration patterns of various immune cells in tumours following treatment with live and UV BHV-1 show that both viruses induce similar proportions of the same populations of immune cells, with the exception of neutrophils. This work highlights the potential of non-replicating BHV-1 as an effective immunotherapy and suggests that viral replication may not be necessary for therapeutic efficacy. These findings contribute to our understanding of the mechanisms underlying BHV-1 immunotherapy and provide insights into the immune response elicited by both live and UV-inactivated BHV-1, paving the way for further development of BHV-1-based cancer treatments. | en_US |
dc.language.iso | en | en_US |
dc.title | INACTIVE, BUT NOT INEFFECTIVE: THE THERAPEUTIC POTENTIAL OF NON-REPLICATING BOVINE HERPESVIRUS TYPE-1 | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MS) | en_US |
dc.description.layabstract | Cancer-killing (oncolytic) viruses (OVs) are promising new cancer treatments where a virus can target cancer cells and leave healthy cells unharmed. While OVs partially work by multiplying within cancer cells (replication), they also trigger the immune system to attack the cancer. Our lab and others have suggested that the immune-stimulating capacity of an OV is just as, if not more, important than an OV’s ability to replicate. Our lab’s OV is called Bovine herpesvirus type-1 (BHV-1). This project demonstrated that inactivated BHV-1 (replication-deficient) can still treat the tumours of mice just as well as its replication-competent counterpart. Analyzing the genetic profile of treated tumours suggests that both replicating and non-replicating BHV-1 have similar anti-cancer mechanisms. We also describe the immune cells that are recruited to the tumour when BHV-1 is introduced. By studying BHV-1’s mechanism, we get closer to maximizing its safety and efficacy as a clinical therapy. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Baracuhy_Enzo_M_2024May_MSc.pdf | 1.8 MB | Adobe PDF | View/Open |
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