Document Details
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Document Type |
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Thesis |
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Document Title |
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DEVELOPMENT OF ONCOLYTIC VIROTHERAPY BASED ON RECOMBINANT VESICULAR STOMATITIS VIRUS AGAINST BREAST CANCER CELLS تطوير علاج فيروسي للأورام معتمد على فيروس التهاب الفم الحويصلي المعدل ضد خلايا سرطان الثدي |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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Background and objectives: Breast cancer remains the most common type of cancer diagnosed in women. Oncolytic immunotherapy represents a novel approach to anticancer therapy. This study investigated the possibility of using recombinant rVSV viruses as oncolytic therapies and whether incorporation of hIL12 to rVSVΔM51 could enhance the therapeutic activity against tumors. This study also looked at aspects related to recovered viruses' efficacy to target breast cancer cells.
Methods: The successful constructs were confirmed by restriction digestion, sequencing, plaque assay, RT-PCR, and electron microscopy. Western immunoblot, ELISA, and immunofluorescence staining confirmed the expression of rVSV proteins, including G, M, N, and hIL12.
Results: I successfully constructed and rescued rVSV, rVSVΔM51, and rVSVΔM51-hIL12 viruses as treatment agents against breast cancer. Several cancer cell lines were found to be susceptible to infection and killing by rVSV, rVSVΔM51, and rVSVΔM51-hIL12. Importantly, non-tumorigenic GM38 cells were less sensitive to rVSVΔM51 infection than rVSV. The treatment efficacy of rVSV and rVSVΔM51 was assessed using the B16F10 tumor-bearing C57BL/6J mouse model. The effects of both treatments significantly delayed tumor growth and prolonged survival compared to untreated mice. Furthermore, approximately 5% of NK cells produced IFN-γ in response to stimulation with MCF7-rVSVΔM51, whereas rVSVΔM51-hIL12 increased the level of IFN-γ production by nearly 2-fold. The results indicated that hIL-12-expressing rVSVΔM51 enhanced the functional activity of NK cells compared to rVSVΔM51 measured by IFN-γ production.
Conclusion and Recommendation: I successfully constructed and rescued rVSV, rVSVΔM51, and rVSVΔM51-hIL12 viruses as treatment agents against breast cancer. This study also shows their ability to lyse breast cancer in vitro and in vivo; therefore, they could be used as a novel vaccine platform for cancer immunotherapy. These findings open the window for future therapeutic and clinical approaches to breast cancer management.
Keywords: Cancer immunotherapy, Oncolytic virus, VSV, Treatments development, Interleukin-12. |
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Supervisor |
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Prof. Magdah Ganash |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1445 AH
2023 AD |
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Co-Supervisor |
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Prof. Anwar Hashem |
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Added Date |
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Wednesday, December 27, 2023 |
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Researchers
| رواء حسين عبدالعال | Abdulal, Rwaa Hussin | Researcher | Doctorate | |
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