In our group I dedicate my time to improve reoviruses as an oncolytic agent. Although reoviruses by themselves are already capable to discriminate between normal diploid cells and tumor cells, not all cancer types are equally attacked by the virus and some even resist wild-type reovirus induced cell death. We use two methods for improving reoviruses: 1) bioselection approach and 2) genetic modification. For the bioselection we encourage the virus (which consists of a 10 segmented dsRNA genome) to mutate in tumor cell lines that resist reovirus infection or cell death. We managed to select mutant reoviruses that no longer requires the canonical receptor to infect cells, but rely on sialic acid motifs for entering cells. With a recently developed plasmid-based system to generate de novo reoviruses we created several replication competent reoviruses containing transgenes to investigate different cell death pathways or to induce an immune response to tumor antigens to help with long-term tumor cell clearance.
I started in 1990 as a technician in the group of Prof. Lex van der Eb, involved in a project on the development of gene therapy for Haemophilia A, mainly using retroviruses as tool. In 2008 I had the opportunity to start with the reovirus research leading to my thesis defence in 2015; Tweaking Reovirus T3D to Boost the Oncolytic Potency. As for today I am still working on this research field in the lab of Prof. Rob Hoeben.
• Characterization of a replicating expanded tropism oncolytic reovirus carrying the adenovirus E4orf4 gene.
Kemp V, Dautzenberg IJC, Cramer SJ, Hoeben RC, van den Wollenberg DJM
Gene therapy 2018. PMID: 30013187 DOI: 10.1038/s41434-018-0032-9
• Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy.
Berkeley RA, Steele LP, Mulder AA, van den Wollenberg DJM, Kottke TJ, Thompson J, Coffey M, Hoeben RC, Vile RG, Melcher A, Ilett EJ.
Cancer immunology research 2018. PMID: 30209061 DOI: 10.1158/2326-6066.cir-18-0309
• Replicating reoviruses with a transgene replacing the codons for the head domain of the viral spike.
van den Wollenberg DJ, Dautzenberg IJ, Ros W, Lipińska AD, van den Hengel SK, Hoeben RC
Gene therapy 2015. PMID: 25588743 DOI: 10.1038/gt.2014.126