Modulation of the Tumor Microenvironment by CXCR4 Antagonist-Armed Viral Oncotherapy Enhances the Antitumor Efficacy of Dendritic Cell Vaccines against Neuroblastoma in Syngeneic Mice

Viruses
Marcin P KomorowskiDanuta Kozbor

Abstract

The induction of antitumor immune responses in tumor-bearing hosts depends on efficient uptake and processing of native or modified tumors/self-antigens by dendritic cells (DCs) to activate immune effector cells, as well as the extent of the immunosuppressive network in the tumor microenvironment (TME). Because the C-X-C motif chemokine receptor 4 (CXCR4) for the C-X-C motif chemokine 12 (CXCL12) is involved in signaling interactions between tumor cells and their TME, we used oncolytic virotherapy with a CXCR4 antagonist to investigate whether targeting of the CXCL12/CXCR4 signaling axis in murine neuroblastoma cells (NXS2)-bearing syngeneic mice affects the efficacy of bone marrow (BM)-derived DCs loaded with autologous tumor cells treated with doxorubicin for induction of immunogenic cell death. Here, we show that CXCR4 antagonist expression from an oncolytic vaccinia virus delivered intravenously to mice with neuroblastoma tumors augmented efficacy of the DC vaccines compared to treatments mediated by a soluble CXCR4 antagonist or oncolysis alone. This study is the first demonstration that modulating the tumor microenvironment by an armed oncolytic virus could have a significant impact on the efficacy of DC vaccines, leading...Continue Reading

References

Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·A VanderplasschenG L Smith
Jun 11, 1999·Journal of Pediatric Hematology/oncology·S G DuBoisK K Matthay
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H GeminderA Ben-Baruch
Aug 3, 2004·Journal of Translational Medicine·Ruggero RidolfiGiuseppe Fiorentini
Sep 17, 2004·The Journal of Biological Chemistry·Brent BerwinSalvatore V Pizzo
Feb 19, 2005·Current Oncology Reports·Pramod K Srivastava
Dec 26, 2006·Nature Medicine·Michel ObeidGuido Kroemer
Feb 28, 2007·Neoplasia : an International Journal for Oncology Research·Libo ZhangSylvain Baruchel
May 4, 2007·The Journal of Clinical Investigation·Eli Gilboa
Oct 28, 2008·Seminars in Immunology·Michelle A NellerChristopher W Schmidt
Dec 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Donald Wong, Walter Korz
Dec 24, 2008·Nature Reviews. Cancer·David H Kirn, Steve H Thorne
Oct 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Margaret GilDanuta Kozbor
Apr 2, 2010·Seminars in Immunology·Cheryl Lai-Lai ChiangGeorge Coukos
Jun 19, 2010·The New England Journal of Medicine·John M Maris
Oct 6, 2010·Biochemical Pharmacology·Beverly A Teicher
Feb 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dan G DudaRakesh K Jain
Dec 22, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kelley A ParatoJohn C Bell
Jun 5, 2012·The British Journal of Oral & Maxillofacial Surgery·M A González-MolesF Esteban
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Margaret GilDanuta Kozbor
Mar 29, 2013·Nature Communications·Jennifer Permuth-WeySimon A Gayther
Jul 6, 2014·Nature Reviews. Cancer·Brian D LichtyJohn C Bell
Oct 17, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Margaret GilDanuta Kozbor
May 6, 2015·Oncoimmunology·Oliver KeppLorenzo Galluzzi
Dec 2, 2015·Drugs·Sarah L Greig
Dec 20, 2017·Oncotarget·Christos FountzilasDevalingam Mahalingam

❮ Previous
Next ❯

Citations

Mar 29, 2019·Expert Opinion on Biological Therapy·Lino E Torres-Domínguez, Grant McFadden
May 17, 2019·Immunotherapy·Parnian JabbariNima Rezaei
Mar 18, 2020·Pharmaceutics·María Julia LambertiJessica Dal Col
Oct 28, 2019·Oncoimmunology·Jenny SprootenAbhishek D Garg
May 7, 2020·Frontiers in Oncology·Lizhi LiJian Ma
Sep 29, 2020·Frontiers in Immunology·Kevin X Liu, Shweta Joshi
Apr 17, 2020·Expert Opinion on Biological Therapy·Adrian PelinRagunath Singaravelu
Dec 22, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Amanda L WoosterDevin B Lowe
Dec 9, 2020·Stem Cells and Development·Caroline HochheuserIlse Timmerman
Dec 25, 2019·Current Opinion in Biotechnology·Erkko Ylösmäki, Vincenzo Cerullo
May 1, 2021·Cancers·Colin H QuinnElizabeth A Beierle
Jul 16, 2021·Frontiers in Immunology·Iris A E van der HoornBerber Piet

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
transfection

Software Mentioned

GraphPad
WinList
GraphPad Prism

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

© 2022 Meta ULC. All rights reserved