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Clinical Cancer Research Vol. 7, 120-126, January 2001
© 2001 American Association for Cancer Research

Experimental Therapeutics, Preclinical Pharmacology

A Conditionally Replicative Adenovirus with Enhanced Infectivity Shows Improved Oncolytic Potency1

Kaori Suzuki, Juan Fueyo, Victor Krasnykh, Paul N. Reynolds, David T. Curiel2 and Ramon Alemany2

Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama 35294 [K. S., V. K., P. N. R., D. T. C., R. A.], and Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [J. F.]

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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