Experimental virotherapy of chemoresistant pancreatic carcinoma using infectivity-enhanced fiber-mosaic oncolytic adenovirus.
Cancer Gene Ther
; 21(7): 264-74, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24903014
Pancreatic cancer is a significant clinical problem and novel therapeutic approaches are desperately needed. Recent advances in conditionally replicative adenovirus-based (CRAd) oncolytic virus design allow the application of CRAd vectors as a therapeutic strategy to efficiently target and eradicate chemoresistant pancreatic cancer cells, thereby improving the efficacy of pancreatic cancer treatment. The goal of this study was to construct and validate the efficacy of an infectivity-enhanced, liver-untargeted, tumor-specific CRAd vector. A panel of CRAds has been derived that embodies the C-X-C chemokine receptor type 4 promoter for conditional replication, two-fiber complex mosaicism for targeting expansion and hexon hypervariable region 7 (HVR7) modification for liver untargeting. We evaluated CRAds for cancer virotherapy using a human pancreatic tumor xenograft model. Employment of the fiber mosaic approach improved CRAd replication in pancreatic tumor xenografts. Substitution of the HVR7 of the Ad5 hexon for Ad serotype 3 hexon resulted in decreased liver tropism of systemically administrated CRAd. Obtained data demonstrated that employment of complex mosaicism increased efficacy of the combination of oncolytic virotherapy with chemotherapy in a human pancreatic tumor xenograft model.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Adenoviridae
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Receptores CXCR4
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Viroterapia Oncolítica
Tipo de estudio:
Clinical_trials
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Cancer Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido