Mitotic Virus Transmission and Immune Responses

Abstract

AbstractThis chapter builds on the mathematical models of oncolytic virus dynamics discussed in the previous chapter and introduces further biological complexity. In extending of the model, we allow for mitotic transmission of the virus, i.e. virus spread through cell division. Depending on the rate at which infected cells divide, we can observe an optimal rate of virus-induced cell killing that minimizes tumor load. Rates of cell killing that are smaller or larger than the optimum lead to higher tumor loads during treatment. In another extension of the model, we introduce immune responses. Anti-viral immune responses can kill infected cells (and thus influence their death rate). Under this assumption, we find an optimal rate of immune-induced cell killing that minimizes tumor load. Less effective immune responses can lead to higher tumor loads through less killing of cells, and too strong of an immune response significantly impairs or eliminates the virus. In addition, a tumor specific immune response is considered that can be activated through virus-induced necrosis of cells. In this case, the effect of virus therapy is augmented and an increase in the strength of anti-tumor immunity is always beneficial for therapy.KeywordsAnti-viral immune responsesOncolytic virusesViral transmission pathwaysMitotic transmissionVertical transmissionOrdinary differential equationsTumor antigen Optimal viral cytotoxicityTumor loadVirus-specific CTLTumor-specific CTL