@article{0f3addc7c924414cbe6cd9d6628b421d,
title = "The organotypic multicellular spheroid is a relevant three-dimensional model to study adenovirus replication and penetration in human tumors in vitro",
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.",
keywords = "Adenovirus, Cancer gene therapy, In vitro model, Oncolytic viruses, Replication, Spheroid",
author = "Jacques Grill and Lamfers, {Martine L.M.} and {Van Beusechem}, {Victor W.} and Dirven, {Clemens M.} and Pherai, {D. Shareen} and Mathijs Kater and {Van Der Valk}, Paul and Ronald Vogels and Vandertop, {W. Peter} and Pinedo, {Herbert M.} and Curiel, {David T.} and Gerritsen, {Winald R.}",
note = "Funding Information: We thank Peter Sminia and Ricardo Feller (both of VU University Medical Center) for sharing their experience with glioma spheroids; Angelique Leonhart (VU University Medical Center) for expertise in immunohistochemistry; and Igor Dmitriev (University of Alabama at Birmingham) for providing anti-CAR monoclonal antibodies. This work was supported by a mobility grant from the Fondation de France/F{\'e}d{\'e}ration Nationale des Centres de Lutte Contre le Cancer N°99005059 to J.G., the Spinoza Award to H.M.P., and grants from the National Cancer Institute number RO1 HLDK-50277, RO1 CA-74242, and RO1 CA-68245 to D.T.C. The research of V.W.v.B. has been made possible by a fellowship of the Royal Dutch Academy of Arts and Sciences. The collaboration between France and The Netherlands is also supported by an INSERM/ZonMW grant for 2002.",
year = "2002",
month = nov,
day = "1",
doi = "10.1016/S1525-0016(02)90713-6",
language = "English",
volume = "6",
pages = "609--614",
journal = "Molecular Therapy",
issn = "1525-0016",
number = "5",
}