ADP-overexpressing adenovirus elicits enhanced cytopathic effect by induction of apoptosis

Cancer Gene Therapy
Chae-Ok YunJoo-Hang Kim

Abstract

Replication-competent adenoviruses (Ad's) are emerging as a promising new modality for treatment of cancer. Selective replication of viral agents in tumor may lead to improved efficacy over nonreplicating Ad's due to their inherent ability to multiply, lyse, and spread to surrounding cells. We have previously shown that an E1B 55 kDa-deleted adenovirus (YKL-1) exhibits tumor-specific replication and cell lysis, but its cytolytic effects were reduced in comparison to the wild-type adenovirus. To increase the oncolytic potency of YKL-1, we have reintroduced the Ad death protein (ADP) gene under the control of either a CMV or an MLP promoter at the E3 region of YKL-1, generating YKL-cADP and YKL-mADP Ad's, respectively. ADP is an 11.6 kDa protein encoded by the E3 transcription unit, and is required to kill adenovirus-infected cells efficiently. However, to date, the mechanism by which ADP mediates cell death has not been clearly defined. In this study, we report that ADP-overexpressing Ad markedly enhanced cytolytic effect (up to 100-fold) against all tumor cell lines tested, but did not increase cytopathic effect in normal skin fibroblast, BJ. Moreover, plaque size formed by YKL-cADP was substantially larger than that of YKL-1, ...Continue Reading

References

Jul 10, 1999·Immunological Reviews·J A Mahr, L R Gooding
Aug 17, 1999·Current Opinion in Immunology·W S WoldA E Tollefson
Feb 2, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J NemunaitisJ Roth
Oct 31, 2000·International Journal of Cancer. Journal International Du Cancer·H LeeJ H Kim
Aug 22, 2002·Cancer Gene Therapy·Jaesung KimChae-Ok Yun

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Citations

Feb 7, 2009·Cancer Gene Therapy·J J Cody, J T Douglas
Sep 10, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jing-Hua HuangChae-Ok Yun
Aug 25, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cristina Puig-SausManel Cascalló
Jan 18, 2012·Human Gene Therapy·Taeyoung KooChae-Ok Yun
Oct 19, 2006·Journal of the National Cancer Institute·Joo-Hang KimChae-Ok Yun
Dec 9, 2010·Nucleic Acids Research·Taco G UilRob C Hoeben
Jan 28, 2006·Journal of Virology·T SubramanianG Chinnadurai
Oct 11, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Joung-Woo ChoiSung Wan Kim
Jun 26, 2014·The Journal of Gene Medicine·Se-Hui JungHamidreza Ghandehari
May 7, 2015·International Journal of Cancer. Journal International Du Cancer·Il-Kyu ChoiChae-Ok Yun
Feb 17, 2015·Genes & Diseases·I V UlasovA Y Baryshnikov
Apr 10, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yoon-A KangChae-Ok Yun
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ji Young YooChae-Ok Yun
Sep 21, 2017·International Journal of Cancer. Journal International Du Cancer·Yan LiChae-Ok Yun
Apr 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eduardo G CafferataOsvaldo L Podhajcer
Oct 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Young-Sook LeeChae-Ok Yun

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