Doctoral Degrees (Mathematical Sciences)

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Browsing Doctoral Degrees (Mathematical Sciences) by browse.metadata.advisor "Eladdadi, Amina"

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    Mathematical Modelling of Tumour-Immune Interactions and Cancer Therapy
    (Stellenbosch : Stellenbosch University, 2017-12) Mahasa, Khaphetsi Joseph; Ouifki, Rachid; Eladdadi, Amina; Stellenbosch University. Faculty of Science. Dept. of Mathematical Sciences. Division Mathematics.
    ENGLISH ABSTRACT : The immune system plays a key role against the development and progression of tumor cells mainly because of its capability of recognizing and destroying cancerous cells. While incredible research efforts have been made over the past decades to decipher the complexity of the tumor-immnue interactions, there is still a lack of a definite and complete picture of these interactions. This may be attributed to the fact that tumor cells develop intricate mechanisms to evade detection and control by the immune system and resist treatments. Although this has been attributed to tumor escape from the immune system, no quantitative studies have been made to precisely characterize key tumor evasion mechanisms from immune surveillance. There is a growing need for new modeling approaches that take into account the complexity of immune system response and/or tumor escape mechanisms, and the recent advances in cancer therapy. This lack has motivated the work in this thesis. We focused our research on addressing the following three scientific questions: (1) How do tumors evolve by escaping immune surveillance? (2) How can oncolytic virus infection of some normal cells in the vicinity of tumor cells enhance oncolytic virotherapy? (3) How can the use of cell carriers for the delivery of oncolytic virus particles to tumor sites affect the outcomes of oncolytic virotherapy in the presence of active immune response? To address these major questions, we have devised three novel mathematical models to study the behaviour of tumor cells following their interactions with key cytotoxic immune cells and oncolytic viruses. The results herein this thesis show the development of immunoresistant phenotype by tumor cells to effectively evade the immune system. This thesis supports the natural killer (NK) cell-based immunotherapeutic approaches that are aimed at enhancing the immune surveillance of tumors. Our work also highlights an interesting possibility of infecting some normal cells in the vicinity of tumor cells to increase the oncolytic infectious titers within tumor microenvironment. Additionally, our findings provide pertinent information on how the use of certain cell carriers may enhance oncolytic virotherapy in the presence of effective immune response within the tumor microenvironment.