Development of a safe treatment for breast cancer using an oncolytic Coxsackievirus B3
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Bahreyni, Amirhossein
issued: 2024-08-01T21:55:58Z
issued: 2024
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Breast cancer poses a significant global challenge, impacting millions worldwide. Despite significant progress in understanding and treating it, there is still a critical need for more effective approaches due to the heterogeneity of breast cancer. Our lab previously developed a safe variant of Coxsackievirus B3 (CVB3), namely microRNA-modified CVB3 (miR-CVB3), with remarkable antitumor activity against lung cancer. In this thesis, I aimed to assess the safety and efficacy of miR-CVB3 in breast cancer therapy. Additionally, I sought to develop a safe platform capable of delivering multiple therapeutic agents, including miR-CVB3, to breast cancer cells. My hypothesis is that miR-CVB3, encapsulated into modified extracellular vesicles, is an excellent candidate for development into a novel oncolytic virotherapy for breast cancer. When applied, miR-CVB3 utilized miR sequences to selectively target cancerous cells while sparing healthy tissue. In vivo experiments revealed promising outcomes, with miR-CVB3 effectively reducing tumor size in mice bearing 4T1 breast tumors. Moreover, miR-CVB3 treatment led to increased immune cell infiltration within the tumor microenvironment, all while maintaining superior safety compared to its parent virus, CVB3. Furthermore, combining miR-CVB3 with additional therapeutic elements such as melittin and CpG sequences significantly enhanced immunogenic cell death in tumor cells. This combination therapy not only enhanced immune cell infiltration but also exhibited efficacy against both primary and distant tumors. Additionally, I showed that miR-CVB3 was able to modify proteins within cancer cells and exosomes, transforming them into immunostimulatory molecules and generating a pro-immune environment within the tumor. To optimize delivery, I harnessed exosomes as carriers for miR-CVB3. These exosomes, released from miR-CVB3-infected cancer cells, contained miR-CVB3 and efficiently transported it to other breast cancer cells. Further modifi…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/88845
note: DEVELOPMENT OF A SAFE TREATMENT FOR BREAST CANCER USING ONCOLYTIC COXSACKIEVIRUS B3 by Amirhossein Bahreyni B.Sc., Mashhad Azad University, 2014 M.Sc., Mazandaran University of Medical Sciences, 2017 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pathology and Laboratory Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2024 © Amirhossein Bahreyni, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Development of a safe treatment for breast cancer using an oncolytic Coxsackievirus B3 submitted by Amirhossein Bahreyni in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pathology and Laboratory Medicine Examining Committee: Dr. Honglin Luo, Professor, Pathology and Laboratory Medicine, UBC Supervisor Dr. Jayachandran Kizhakkedathu, Professor, Pathology and Laboratory Medicine, UBC Supervisory Committee Member Dr. Pascal Bernatchez, Associate Professor, Anesthesiology, Pharmacology and Therapeutics, UBC Supervisory Committee Member Dr. Xiaoyan Jiang , Professor , Department of Medical Genetics, UBC University Examiner Dr. Christopher Maxwell , Professor, Department of Pediatrics, UBC University Examiner Additional Supervisory Committee Members: Dr. Xuesen Dong , Associate Professor, Department of Urologic Sciences, UBC Supervisory Committee Member iii Abstract Breast cancer poses a significant global challenge, impacting millions worldwide. Despite significant progress in understanding and treating it, there is still a critical need for more effective approaches due to the heterogeneity of breast cancer. Our lab previously developed a safe variant of Coxsackievirus B3 (CVB3), namely microRNA-modified CVB3 (miR-CVB3), with remarkable antitumor activity against lung cancer. In this thesis, I aimed to as…
has type: Thesis/Dissertation
date issued: 2024-11
is shown at: 10.14288/1.0444965
language: eng
degree discipline: Pathology and Laboratory Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Luo, Honglin
type: Text
identifier URI: http://hdl.handle.net/2429/88845