Oncolytic adenovirus therapy is believed to be a promising way to treat cancer patients. To be able to target tumor cells with an oncolytic adenovirus, expression of the adenovirus receptor on the... Show moreOncolytic adenovirus therapy is believed to be a promising way to treat cancer patients. To be able to target tumor cells with an oncolytic adenovirus, expression of the adenovirus receptor on the tumor cell is essential. Different adenovirus types bind to different receptors on the cell, of which the expression can vary between tumor types. Pre-existing neutralizing immunity to human adenovirus species C type 5 (HAdV-C5) has hampered its therapeutic efficacy in clinical trials, hence several adenoviral vectors from different species are currently being developed as a means to evade pre-existing immunity. Therefore, knowledge on the expression of appropriate adenovirus receptors on tumor cells is important. This could aid in determining which tumor types would benefit most from treatment with a certain oncolytic adenovirus type. This review provides an overview of the known receptors for human adenoviruses and how their expression on tumor cells might be differentially regulated compared to healthy tissue, before and after standardized anticancer treatments. Mechanisms behind the up- or downregulation of adenovirus receptor expression are discussed, which could be used to find new targets for combination therapy to enhance the efficacy of oncolytic adenovirus therapy. Additionally, the utility of the adenovirus receptors in oncolytic virotherapy is examined, including their role in viral spread, which might even surpass their function as primary entry receptors. Finally, future directions are offered regarding the selection of adenovirus types to be used in oncolytic adenovirus therapy in the fight against cancer. Show less
Non-human primate (NHP)-derived adenoviruses have formed a valuable alternative for the use of human adenoviruses in vaccine development and gene therapy strategies by virtue of the low... Show moreNon-human primate (NHP)-derived 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 proffers the question whether NHP-derived adenoviruses could also be employed for viral oncolysis in human patients. While vaccine vectors are conventionally made as replication-defective vectors, in oncolytic applications replication-competent viruses are used. The data on NHP-derived adenoviral vectors obtained from vaccination studies can only partially support the suitability of NHP-derived adenoviruses for use in oncolytic virus therapy. In addition, the use of NHP-derived adenoviruses in humans might be received warily given the recent zoonotic infections with influenza viruses and coronaviruses. In this review, we discuss the similarities and differences between human- and NHP-derived adenoviruses in view of their use as oncolytic agents. These include their genome organization, receptor use, replication and cell lysis, modulation of the host's immune responses, as well as their pathogenicity in humans. Together, the data should facilitate a rational and data-supported decision on the suitability of NHP-derived adenoviruses for prospective use in oncolytic virus therapy. Show less
