RT Journal Article
T1 A Novel Approach Using Transcomplementing Adenoviral Vectors for Gene Therapy of Adrenocortical Cancer
A1 Wolkersdörfer, G. W.
A1 Bornstein, S. R,
A1 Higginbotham, J. N.
A1 Hiroi, N.
A1 Vaquero López, Juan José
A1 Green, M. V.
A1 Blaese, R. M.
A1 Aguilera, G.
A1 Chrousos, G. P.
A1 Ramsey, W. J.
AB Current therapies for adrenocortical carcinomas do not improvethe life expectancy of patients. I n this study, we tested whether agene-transfer therapy based upon a suicide gene/prodrug systemwould be effective in an animal model of the disease. We employedE4- and ElA/B-depleted. herpes simplex virus-thymidinekinase-expressing adenoviral mutants that transcomplementeach other within tumor cells, hereby improving transgene deliveryand efficacy by viral replication in situ. Transcomplementationof vectors increased the fraction of transduced of tumorcells. This increase was accompanied by greater tumor volumereduction compared to non-transcomplementing approaches.Survival time improved with non-replicating vectors plus GCVcompared to controls. However, transcomplementation/replicationof vectors led to a further significant increment in anti-tumoractivity and survival time (p <0.02). In treated animals, weobserved a high number of apoptotic nuclei both adjacent toand distant from injection sites and sites of viral oncolysis. Ultrastructuralanalyses exhibited nuclear inclusion bodies characteristicof virus production in situ, and provided further evidencethat this therapy induced apoptotic cell death within tumor cells.We conclude that the efficacy of suicide gene therapy is significantlyamplified by viral replication and, in combination withGCV, significantly reduces tumor burden and increases survivaltime.
PB Thieme Publishing
SN 0018-5043 (print version)
SN 1439-4286 (online version)
YR 2002
FD 2002-06
LK https://hdl.handle.net/10016/14994
UL https://hdl.handle.net/10016/14994
LA eng
DS e-Archivo
RD 20 may. 2024