Abstract |
The absence or the presence of low levels of the Coxsackievirus and adenovirus receptor (CAR) on several tumor types might limit the efficacy of recently proposed tumor-specific or conditionally replicative adenoviruses (CRAds). To address this issue, we used a genetic modification of the fiber knob in the context of an E1A-defective CRAd to allow CAR-independent target cell infection as a means to enhance oncolytic potency. Such infectivity-enhanced CRAd showed higher replication, more efficient infection, and lysis of tumor cells in vitro. Of note, the improved antitumor effect of the fiber-modified CRAd could be demonstrated in vivo. We conclude that the combination of genomic modification to achieve tumor-selective replication and capsid modification to enhance infectivity yields more potent oncolytic adenoviruses for use in cancer treatment.
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Authors | K Suzuki, J Fueyo, V Krasnykh, P N Reynolds, D T Curiel, R Alemany |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 7
Issue 1
Pg. 120-6
(Jan 2001)
ISSN: 1078-0432 [Print] United States |
PMID | 11205899
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Adenovirus E1A Proteins
- Formazans
- Oligopeptides
- Retinoblastoma Protein
- 1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan
- arginyl-glycyl-aspartic acid
- Luciferases
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Topics |
- Adenoviridae
(genetics, immunology, physiology)
- Adenovirus E1A Proteins
- Animals
- Cell Division
(drug effects)
- Female
- Formazans
- Genetic Vectors
- Humans
- Immunologic Tests
- In Vitro Techniques
- Luciferases
(metabolism)
- Lung Neoplasms
(therapy, virology)
- Male
- Mice
- Mice, Nude
- Oligopeptides
(metabolism)
- Prostatic Neoplasms
(therapy, virology)
- Retinoblastoma Protein
(genetics, metabolism)
- Time Factors
- Transplantation, Heterologous
- Tumor Cells, Cultured
(virology)
- Virus Replication
- Viruses
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