Intracellular and immune-response delays effects on the interation between tumor cells, oncolytic viruses and the immune system

Winnie Wanja, Chabaari (2019-12)

Thesis (MSc)--Stellenbosch University, 2019.

Thesis

ENGLISH ABSTRACT: Lately, oncolytic viruses have been used to mitigate cancer as they lyse tumor cells whilst leaving normal cells largely unharmed (as opposed to many other forms of cancer treatment). The oncolytic effect depends on both viral replication ability and immune response type induced by said replication. A major challenge posed by this therapy is any potential delay that can occur during viral replication, combined with a fast immune response. For this project, we will investigate possible trade-offs of the interactions, with particular focus on the effect(s) of delay.We will extend recently published mathematical models on virotherapy by taking into account the simultaneous effect of the delay and considering various forms of virus-cell infections. We perform stability analysis with the delay and run numerical simulations to confirm the mathematical findings and see how well this model would fit data or whether by the introduction of the delay terms, we improve the fit of the data. Eventually, we derive an explicit formula for the trade-off between the two delays that leads to tumor eradication. One of the main findings is the occurrence of a delay-induced Hopf bifurcation, indicative of tumor relapse which is a confirmation of other previous cancer virotherapy mathematical models.

AFRIKAANSE OPSOMMING: Onkolitiese virusse word die afgelope tyd gebruik om kanker te versag, aangesien hulle tumorselle lig, terwyl normale selle grootliks ongedeerd bly (in teenstelling met baie ander vorme van kankerbehandeling). Die onkolitiese effek is afhanklik van sowel die virale replikasievermoë as die immuun-re-sponse tipe wat deur genoemde replikasie veroorsaak word. 'n Groot uitdaging wat hierdie terapie inhou, is die potensiële vertraging wat tydens virusreplikasie kan voorkom, gekombineer met 'n vinnige immuunreaksie. Vir hierdie projek ondersoek ons moontlike inruilings van die interaksies, veral met die oog op die gevolge van vertraging. Ons brei wiskundige modelle oor viroterapie wat onlangs gepubliseer is, uit deur die gelyktydige effek van die vertraging en die oorweging van verskillende vorme van virusselinfeksies in ag te neem. Ons doen stabiliteitsanalise met die vertraging en voer numeriese simulasies uit om die wiskundige bevindings te bevestig en te bepaal hoe goed hierdie model by die data sou pas, of deur die inwerkingtreding van die vertragingsterme die pas van die data te verbeter. Uiteindelik verkry ons 'n eksplisiete formule vir die verhandeling tussen die twee vertragings wat lei tot die uitwissing van gewasse. Een van die belangrikste bevindings is die voorkoms van 'n vertraging-geïnduseerde Hopf-bifurkasie, wat 'n aanduiding is van tumorterugval, wat die bevestiging is van ander vorige wiskundige modelle vir kankerviroterapie.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/106928
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