Rob Hoeben has a keen interest in development and clinical translation of viral tools for gene and stem cell therapy. He has a long-term expertise in viruses for gene therapy. Initially his work focused on retrovirus and adenovirus-derived vectors for gene therapy of hemophilia A. In parallel, he generated new cell lines for the production of adenoviruses, such as the 911 cell line for production of research grade viruses and, in collaboration with scientist at Crucell, the PER.C6 cell line for clinical grade products. Later he embraced the use of mammalian reoviruses. His lab pioneered a strategy for their genetic modification allowing the construction of a replication-competent genetically retargeted reovirus.
He have two interdependent research goals. Firstly, the ambition is to improve both the specificity and the efficiency of the oncolytic viruses. While many viruses have an intrinsic tumour-cell preference we aim at improving their tumour-cell specificity by either genetic modification or by bioselection. The latter approach recently yielded oncolytic reoviruses that can infect cells independent of the reovirus receptor JAM-A. This is of relevance because the JAM-A- expression is frequently down-regulated in tumour cells. The ambition is to generate an oncolytic reovirus that will be evaluated clinically.
In parallel we aim at understanding the mechanisms underlying the viruses’ preference for infecting and killing tumour cells. In the latter research lines we selected cytolytic viruses that infect chemo- and radiation-resistant tumour cells (i.e. gioma and Ewing sarcoma cell lines). These mutants are active in a broad panel of tumor cells. We exploit the new viruses for elucidating which cell-death pathways can still be activated in the resistant cell lines. The results provide insight that may allow the identification of new druggable cell-death pathways.
Hoeben is a graduate of Utrecht University (Biology) and performed his PhD research at Leiden University in the lab. of prof. Van der Eb in collaboration with prof. Briët. Here he developed viral gene-transfer vectors for gene therapy of haemophilia A. After his graduation he developed a research interest in cancer gene therapy and viral strategies of immune evasion. After various post-doctoral positions in Leiden, he was appointed as a professor at the Leiden University and Leiden University Medical Center in 2000, and heads the Virus and Stem Cell Biology lab.
Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes.
Kracht MJ, Van Lummel M, Nikolic T, Joosten AM, Laban S, Van der Slik AR, Van Veelen PA, Carlotti F, De Koning EJ, Hoeben RC, Zaldumbide A, Roep BO
Nat Med 23, 501-507. 2017
Replicating reoviruses with a transgene replacing the codons for the head domain of the viral spike.
Van den Wollenberg DJ, Dautzenberg IJ, Ros W, Lipinska AD, Van den Hengel SK, Hoeben RC
Gene Ther 22, 267-279. 2015
Genetically engineered human islets protected from CD8-mediated autoimmune destruction in vivo.
Zaldumbide A, Alkemade G, Carlotti F, Nikolic T, Abreu JR, Engelse MA, Skowera A, De Koning EJ, Peakman M, Roep BO, Hoeben RC, Wiertz EJ
Mol Ther 21, 1592-1601. 2013