Back to Search
Start Over
The role of cyclophosphamide in enhancing antitumor efficacy of an adenovirus oncolytic vector in subcutaneous Syrian hamster tumors
The role of cyclophosphamide in enhancing antitumor efficacy of an adenovirus oncolytic vector in subcutaneous Syrian hamster tumors
- Source :
- Cancer gene therapy
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- We have previously reported that intratumoral injection of VRX-007--an Ad5 (a species C adenovirus)-based vector overexpressing adenovirus death protein--can suppress the growth of subcutaneous HaK (hamster renal cancer) tumors. VRX-007 replication and tumor growth inhibition are enhanced when the hamsters are immunosuppressed by a high dose of cyclophosphamide (CP), an immunosuppressive and chemotherapeutic agent. Here, we report that continuous immunosuppression with CP was not required for increased oncolytic activity of VRX-007 because short-term dosing or continuous dosing with the drug yielded similar antitumor results. Prolonged viral replication was found only in animals on continuous CP treatment. We used 007-Luc, a replication-competent, luciferase-expressing vector similar to VRX-007, to investigate the replication of the vector over time. Tumor growth inhibition was similar in hamsters given CP treatment either 1 week before or 1 week after 007-Luc injection, which suggests that CP exerts its antitumor efficacy independently of vector therapy. 007-Luc did not spread far from the inoculation site, even in immunosuppressed, CP-treated animals. Our results indicate that the enhanced effectiveness that is produced by the combination of VRX-007 and CP therapies is due to their two independent mechanisms and that they do not have to be given simultaneously for the improved outcome.
- Subjects :
- tumor
Cancer Research
Cyclophosphamide
medicine.medical_treatment
Genetic Vectors
Gene Expression
Hamster
Pharmacology
Biology
Virus Replication
medicine.disease_cause
Article
Adenoviridae
Genes, Reporter
Cell Line, Tumor
Cricetinae
Neoplasms
Gene Order
medicine
Animals
Humans
Vector (molecular biology)
Antineoplastic Agents, Alkylating
Molecular Biology
Oncolytic Virotherapy
Cancer
Immunosuppression
adenovirus
medicine.disease
hamster
Oncolytic virus
Oncolytic Viruses
Viral replication
Molecular Medicine
cyclophosphamide
Female
virotherapy
medicine.drug
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi.dedup.....2005eb0996e09ce86da6fcb59c689659
- Full Text :
- https://doi.org/10.1038/cgt.2013.49