Conditionally replication-competent adenoviral vectors with enhanced infectivity for use in gene therapy of melanoma

Human Gene Therapy
Yanzheng LiuAlbert Deisseroth

Abstract

To generate vector Ad.Tyr-E1A, which is cytolytic for tyrosinase-positive melanoma cells, we replaced the adenoviral E1A promoter with a human tyrosinase enhancer/promoter. To overcome the low transduction efficiency in populations of melanoma cells that exhibit a low level of the coxsackievirus-adenovirus receptor (CAR), we inserted an RGD-4C peptide into the HI loop of the fiber knob domain of the Ad.Tyr-E1A vector. The resulting vector was named Ad.Tyr-E1A(RGD). As a result of these changes, the transduction efficiency of the RGD-modified vector was increased both in vitro and in vivo. Western blot analysis proved that infection of cells with the Ad.Tyr-E1A(RGD) vector led to expression of the E1A gene selectively in tyrosinase-positive melanoma cell lines, but not in tyrosinase-negative cell lines. The Ad.Tyr-E1A(RGD) vector was as potent in its cytotoxic effect as a tumor nonselective vector (Ad.CMV-E1A) in tyrosinase-positive melanoma cell lines. The Ad.Tyr-E1A(RGD) vector produced a higher vector particle yield in tumor cells than did the Ad.Tyr-E1A vector. Intratumoral injection of the Ad.Tyr-E1A(RGD) vector into xenotransplanted human melanoma tumors led to tumor regression in vivo. The combination of tumor-specific re...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R E SeftorM J Hendrix
Jun 1, 1992·The Journal of Clinical Investigation·B Felding-HabermannD A Cheresh
Feb 5, 1998·CA: a Cancer Journal for Clinicians·S H LandisP A Wingo
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Jun 13, 2001·Biochemical and Biophysical Research Communications·M OhashiM Omata
Mar 28, 2002·Human Gene Therapy·Takafumi NakamuraHirofumi Hamada
Sep 17, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lixin ZhangAlbert Deisseroth
Feb 21, 2004·CA: a Cancer Journal for Clinicians·Ahmedin JemalUNKNOWN American Cancer Society

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Citations

Jan 25, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Dirk M Nettelbeck
Mar 1, 2007·Human Gene Therapy·Yanzheng LiuPer Borgstrom
Apr 28, 2009·Advanced Drug Delivery Reviews·Dominik E Dorer, Dirk M Nettelbeck
Nov 29, 2005·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Kai TemmingRobbert J Kok
Jul 12, 2005·Peptides·Francois Rouzaud, Vincent J Hearing
Feb 9, 2006·Pharmacology & Therapeutics·Pankaj GuptaPaul B Fisher
Sep 30, 2004·Technology in Cancer Research & Treatment·Kenneth Lundstrom

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