Leiden University Scholarly Publications

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Bots, S.T.F. (2023)

Nonhuman primate adenoviruses for use as oncolytic agents

Doctoral Thesis
Nonhuman primate adenoviruses have formed a valuable alternative for the use of human adenoviruses in vaccine development and gene therapy strategies by virtue of the low seroprevalence of neutralizing immunity in the human population. The more recent use of several human adenoviruses as oncolytic agents has exhibited excellent safety profiles and firm evidence of clinical efficacy. This raises the question whether nonhuman primate adenoviruses could also be employed for viral oncolysis in human patients. The research in this thesis provides a rational and data-supported decision on the use of nonhuman primate adenoviruses as a base for the development of new oncolytic derivatives with limited neutralizing immunity in the human population. Moreover, the development of a potent new gorilla-derived oncolytic adenovirus named GoraVir shows the feasibility of the approach. Hopefully, this research provides some reassurance regarding the future use of replication-competent nonhuman...Show moreNonhuman primate adenoviruses have formed a valuable alternative for the use of human adenoviruses in vaccine development and gene therapy strategies by virtue of the low seroprevalence of neutralizing immunity in the human population. The more recent use of several human adenoviruses as oncolytic agents has exhibited excellent safety profiles and firm evidence of clinical efficacy. This raises the question whether nonhuman primate adenoviruses could also be employed for viral oncolysis in human patients. The research in this thesis provides a rational and data-supported decision on the use of nonhuman primate adenoviruses as a base for the development of new oncolytic derivatives with limited neutralizing immunity in the human population. Moreover, the development of a potent new gorilla-derived oncolytic adenovirus named GoraVir shows the feasibility of the approach. Hopefully, this research provides some reassurance regarding the future use of replication-competent nonhuman primate adenovirus vectors as therapeutic agents.
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Adenovirus
Nonhuman primate
Oncolytic virus
Cancer
Pancreatic ductal adenocarcinoma
All authors
Bots, S.T.F.
Supervisor
Hoeben, R.C.
Co-supervisor
Kemp, V.
Committee
Burg, S.H. van der: Heemskerk, M.H.M.; Snijder, E.J.; Eijck, C.H.J. van; Lamfers, M.L.M.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2023-06-21
ISBN (print)
9789464831443

Funding

Sponsorship
Stichting Overleven met Alvleesklierkanker