Abstract
The use of adenoviruses for gene transfer and as oncolytic agents is currently receiving wide-spread attention. As specific constraints to adenovirus distribution and spread cannot be studied in cell cultures, there is a need for an in vitro three-dimensional (3D) model mimicking the in vivo biology of tumors. We studied the interactions between tumor and adenoviruses using multicellular spheroids grown from primary brain tumor material. Using β-galactosidase and luciferase reporter genes expressed by replication-defective adenoviruses, we showed that infection was restricted to the first layer of cells. Using a replication-competent adenovirus expressing the luciferase gene, was showed that transgene expression in the spheroid was considerably enhanced and that viral spreading deep into the 3D structure took place. In addition, a tetrazolium salt-based metabolic assay could be used to compare the oncolytic activity of different concentrations of replication-competent adenoviruses. We can conclude that organotypic spheroids offer a versatile in vitro system for studying distribution, spread, and oncolysis by adenoviruses in a clinically relevant model.
Original language | English |
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Pages (from-to) | 609-614 |
Number of pages | 6 |
Journal | Molecular Therapy |
Volume | 6 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Nov 2002 |
Keywords
- Adenovirus
- Cancer gene therapy
- In vitro model
- Oncolytic viruses
- Replication
- Spheroid