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[Cancer Research 61, 6377-6381, September 1, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Targeting Oncolytic Adenoviral Agents to the Epidermal Growth Factor Pathway with a Secretory Fusion Molecule1

Akseli Hemminki2, Igor Dmitriev, Bin Liu, Renee A. Desmond, Ramon Alemany and David T. Curiel

Division of Human Gene Therapy, Departments of Medicine, Pathology, and Surgery, and the Gene Therapy Center [A. H., I. D., B. L., R. A., D. T. C.], and Comprehensive Cancer Center Biostatistics Unit [R. A. D.], University of Alabama at Birmingham, Birmingham, Alabama 35294-3300

Cancer gene therapy with conditionally replicating adenoviruses is a powerfulway of overcoming low tumor transduction. However, one of the main remaining obstacles is the highly variable level of the coxsackie-adenovirus receptor expression on human primary cancers. In contrast, the epidermal growth factor receptor (EGFR) is overexpressed in various tumor types, and its expression correlates with metastatic behavior and poor prognosis. We constructed an adenovirus expressing a secretory adaptor capable of retargeting adenovirus to EGFR, resulting in a more than 150-fold increase in gene transfer. A replication-competent dual-virus system secreting the adaptor displayed increased oncolytic potency in vitro and therapeutic gain in vivo. This approach could translate into increased efficacy and specificity in the treatment of EGFR overexpressing human cancers.




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Copyright © 2001 by the American Association for Cancer Research.