Defining the mechanisms underlying cell-mediated delivery of oncolytic viruses to tumors

Abstract

Oncolytic viruses are often eliminated by the immune system before they arive at tumor sites. The use of carrier cells is a method to improve the efficiency of oncolytic viruses. These cells carry the virus to tumors while shielding it from the immune system. Various cell types can be used as carrier cells, including leukocytes, progenitor cells, sickle red blood cells, and tumor cells, all four of which are discussed in this thesis. As the therapeutic efficiency of carrier cells is still limited though, improvement is necessary. Elucidation of the factors underlying the migration of the different carrier cell types can contribute to a better therapeutic efficiency. Here, an overview is provided of the various factors involved in carrier cell migration, such as cytokines, chemokines, and adhesion molecules. As tumor cells adjust their properties to evade from the immune system and from anti-tumor therapies, generating oncolytic viruses that target a broader range of tumor cells likely increases the potential of oncolytic viruses too. Here, experiments have been performed demonstrating that a previously generated oncolytic reovirus mutant is able to infect and destroy a broader range of tumor types than wildtype reovirus.