Enhancing reovirus for use in oncolytic virotherapy

Kemp, V. (2019)

Doctoral Thesis

Oncolytic reovirus has the natural preference to kill transformed cells while sparing normal cells. Its administration has been shown to be safe in clinical trials, but the anti-cancer efficacy remains to be improved. In this thesis, we discuss several aspects that are important for the design of a potent anti-cancer therapeutic strategy using reovirus. We explored which cellular factors and pathways are important for efficient reovirus replication. Furthermore, we genetically modified the reovirus genome to encode potentially therapeutic transgenes. We tested the potency of these recombinant reoviruses, and describe what we believe is the most promising strategy to move forward. Moreover, we discuss the stability issues that we encountered during the generation of recombinant reoviruses. Finally, we discuss the various challenges and opportunities in how to proceed.

• Reovirus
• Oncolytic
• Cancer
• Autophagy
• Transgene

• All authors: Kemp, V.
• Supervisor: Hoeben, R.C.
• Co-supervisor: Wollenberg, D.J.M. van den
• Committee: Meijer, J.H.; Hall, T. van; Reggiori, F.M.; Eijck, C.H.J. van
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine / Leiden University Medical Center (LUMC), Leiden University
• Date: 2019-02-07
• ISBN (print): 9789463324403