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Oncolytic activity of p53-expressing conditionally
replicative adenovirus AdDelta24-p53 against human malignant glioma
Geoerger B, Vassal G, Opolon P, Dirven CM, Morizet J, Laudani L, Grill J,
Giaccone G, Vandertop WP, Gerritsen WR, van Beusechem VW
Department of Pediatrics, Institut Gustave Roussy, Villejuif, France.
Prognosis of malignant glioma is poor, and results of treatment remain mediocre.
Conditionally replicative adenoviruses hold promise as alternative anticancer
agents for the treatment of malignant glioma.
Here, we evaluated the
conditionally replicative adenovirus AdDelta24 and its recently developed
derivative AdDelta24-p53, which expresses functional p53 tumor suppressor
protein while replicating in cancer cells, for treatment of malignant glioma.
In
comparison to its parent AdDelta24, AdDelta24-p53 killed most malignant glioma
cell lines and primary glioblastoma multiforme short-term cultures more
effectively, irrespective of their p53 status.
Moreover, AdDelta24-p53 caused
more frequent regression and more delayed growth of IGRG121 xenografts derived
from a glioblastoma multiforme in vivo.
Five intratumoral injections of 10(7)
pfu AdDelta24 gave 24 days median tumor growth delay (P < 0.01), 30% tumor
regressions, and 30% animals surviving >120 days tumor-free or with a minimal
tumor residual.
The same dose of AdDelta24-p53 caused >113 days of median
tumor growth delay (P < 0.001), 70% tumor regressions, and 60% animals
surviving >120 days tumor-free or with a minimal tumor residual.
Antitumor
effects in vivo were associated with extensive conditionally replicative
adenovirus replication, apoptosis induction, and tumor morphology changes,
including dissociation, inflammatory cell infiltration, and necrosis.
We
conclude that conditionally replicative adenoviruses expressing p53 are
promising new agents for treatment of malignant glioma.
PMID: 15313916 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15313916
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