A Conditionally Replicative Adenovirus with Enhanced Infectivity Shows Improved Oncolytic Potency

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...

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Bibliographic Details
Published in:Clinical cancer research 2001-01, Vol.7 (1), p.120-126
Main Authors: SUZUKI, Kaori, FUEYO, Juan, KRASNYKH, Victor, REYNOLDS, Paul N, CURIEL, David T, ALEMANY, Ramon
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - immunology
Adenoviridae - physiology
Adenovirus E1A Proteins
Animals
Antineoplastic agents
Biological and medical sciences
Cell Division - drug effects
Chemotherapy
Female
Formazans
Genetic Vectors
Humans
Immunologic Tests
In Vitro Techniques
Luciferases - metabolism
Lung Neoplasms - therapy
Lung Neoplasms - virology
Male
Medical sciences
Mice
Mice, Nude
Oligopeptides - metabolism
Pharmacology. Drug treatments
Prostatic Neoplasms - therapy
Prostatic Neoplasms - virology
Retinoblastoma Protein - genetics
Retinoblastoma Protein - metabolism
Time Factors
Transplantation, Heterologous
Tumor Cells, Cultured - virology
Virus Replication
Viruses
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Summary: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.
ISSN:1078-0432
1557-3265