Treg depletion-enhanced IL-2 treatment facilitates therapy of established tumors using systemically delivered oncolytic virus.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Timothy KottkeRichard Vile

Abstract

There are several roadblocks that hinder systemic delivery of oncolytic viruses to the sites of metastatic disease. These include the tumor vasculature, which provides a physical barrier to tumor-specific virus extravasation. Although interleukin-2 (IL-2) has been used in antitumor therapy, it is associated with endothelial cell injury, leading to vascular leak syndrome (VLS). Here, we demonstrate that IL-2-mediated VLS, accentuated by depletion of regulatory T cells (Treg), facilitates localization of intravenously (i.v.) delivered oncolytic virus into established tumors in immune-competent mice. IL-2, in association with Treg depletion, generates "hyperactivated" natural killer (NK) cells, possessing antitumor activity and secreting factors that facilitate virus spread/replication throughout the tumor by disrupting the tumor architecture. As a result, the combination of Treg depletion/IL-2 and systemic oncolytic virotherapy was found to be significantly more therapeutic against established disease than either treatment alone. These data demonstrate that it is possible to combine biological therapy with oncolytic virotherapy to generate systemic therapy against established tumors.

References

Dec 24, 1997·Immunopharmacology·R Baluna, E S Vitetta
Jan 5, 2002·Journal of Clinical Laser Medicine & Surgery·R J Lanzafame
Feb 6, 2002·Circulation·Takako NakajimaCornelia M Weyand
Jun 5, 2003·Expert Opinion on Therapeutic Targets·Barbara Fingleton
May 4, 2004·Trends in Molecular Medicine·Brian D LichtyJohn C Bell
May 27, 2004·Blood·Patricia YotndaMalcolm Brenner
Jul 27, 2004·Nature Medicine·Paul GregorevicJeffrey S Chamberlain
Aug 10, 2004·Nature Biotechnology·Gregory A DanielsRichard G Vile
Jan 27, 2005·Viral Immunology·Glen N Barber
Nov 22, 2005·Oncogene·Glen N Barber
Dec 24, 2005·Blood·Yanzheng Liu, Albert Deisseroth
Mar 25, 2006·Science·Steve H ThorneChristopher H Contag
Aug 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Giulia FulciE Antonio Chiocca
Aug 18, 2006·International Immunology·Louise MelencioMitzi Nagarkatti
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anthony T PowerJohn C Bell
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Patrick F KellyDavid A Williams
Jan 11, 2007·Cancer Research·Uma ThanarajasingamRichard G Vile
Feb 15, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elizabeth Kelly, Stephen J Russell
Mar 10, 2007·Current Cancer Drug Targets·John C Bell
Mar 17, 2007·Cancer Research·Rosa Maria DiazRichard G Vile
Jun 2, 2007·Nature Reviews. Drug Discovery·Jialiang HuGhislain Opdenakker
Jul 27, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jin ChengJohn G Hay

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Citations

Mar 26, 2013·Cellular & Molecular Immunology·Isabela Pedroza-PachecoAurore Saudemont
Oct 2, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Timothy KottkeRichard G Vile
Oct 28, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Candice WillmonRichard Vile
Jul 12, 2012·Nature Biotechnology·Stephen J RussellJohn C Bell
Mar 30, 2011·Human Gene Therapy·Elspeth SmithBrian D Lichty
Feb 9, 2012·Advances in Virology·Christopher A Alvarez-BreckenridgeE Antonio Chiocca
Jan 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Timothy KottkeRichard G Vile
Jun 25, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elizabeth IlettRichard Vile
Oct 18, 2008·Expert Review of Anticancer Therapy·Robin J PrestwichFiona Errington
May 9, 2012·Expert Opinion on Biological Therapy·Keith A Lawson, Don G Morris
Nov 18, 2008·Expert Opinion on Investigational Drugs·Timothy A YapJohann S Debono
Aug 28, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Karishma RajaniRichard Vile
Oct 19, 2011·Developmental and Comparative Immunology·Revathi Shanmugasundaram, Ramesh K Selvaraj
Oct 12, 2012·The Journal of General Virology·Eric Hastie, Valery Z Grdzelishvili
Sep 1, 2015·Immunotherapy·Claudia CantoniMassimo Vitale
Apr 8, 2015·Current Opinion in Virology·Christopher A Alvarez-BreckenridgeE Antonio Chiocca
Aug 8, 2014·Frontiers in Oncology·Norman WollerFlorian Kühnel
Jun 27, 2014·Frontiers in Oncology·Andrew NguyenYonghong Wan
Nov 22, 2017·Journal for Immunotherapy of Cancer·Adam Ajina, John Maher
Nov 4, 2008·European Journal of Immunology·Jacques ZimmerFrançois Hentges
Jun 2, 2017·The Open Virology Journal·Tiantian ZhangKarim Essani
Jul 6, 2014·Nature Reviews. Cancer·Brian D LichtyJohn C Bell
Jan 27, 2016·World Journal of Gastroenterology : WJG·Andrea Marie Ibrahim, Yao-He Wang

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