Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment

Molecular Therapy Oncolytics
Maria De LuciaAnna Morena D'Alise

Abstract

Oncolytic viruses (OVs) are novel anti-tumor agents with the ability to selectively infect and kill tumor cells while sparing normal tissue. Beyond tumor cytolysis, OVs are capable of priming an anti-tumor immune response via lysis and cross-presentation of locally expressed endogenous tumor antigens, acting as an "endovaccine." The effectiveness of OVs, similar to other immunotherapies, can be hampered by an immunosuppressive tumor microenvironment. In this study, we modified a previously generated oncolytic herpes simplex virus (oHSV) retargeted to the human HER2 (hHER2) tumor molecule and encoding murine interleukin-12 (mIL-12), by insertion of a second immunomodulatory molecule, murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), to maximize therapeutic efficacy. We assessed the efficacy of this double-armed virus (R-123) compared to singly expressing GM-CSF and IL-12 oHSVs in tumor-bearing mice. While monotherapies were poorly effective, combination with α-PD1 enhanced the anti-tumor response, with the highest efficacy of 100% response rate achieved by the combination of R-123 and α-PD1. Efficacy was T cell-dependent, and the induced immunity was long lasting and able to reject a second contralateral tumor. ...Continue Reading

References

Feb 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·J N ParkerJ M Markert
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie P PiechockiWei-Zen Wei
Oct 2, 2007·International Journal of Pharmaceutics·Yusuke EtoShinsaku Nakagawa
May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Laura MenottiGabriella Campadelli-Fiume
Nov 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neil N SenzerJohn J Nemunaitis
Mar 17, 2010·Cytokine & Growth Factor Reviews·Hiroshi NakashimaE A Chiocca
Mar 2, 2012·Journal of Virology·James M MarkertRichard J Whitley
Mar 9, 2012·Advances in Virology·Mark S FergusonYaohe Wang
Sep 12, 2013·Molecular Cancer·David L BartlettZong Sheng Guo
Oct 19, 2013·The Journal of Infectious Diseases·Heather BradleyGeraldine M McQuillan
May 28, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert H I AndtbackaRobert S Coffin
Jan 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Frederick J Kohlhapp, Howard L Kaufman
Mar 2, 2016·Viruses·Gabriella Campadelli-FiumeValentina Gatta
Jun 15, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Igor PuzanovRobert H I Andtbacka
Feb 9, 2017·Current Cancer Drug Targets·Hiroaki UchidaJoseph C Glorioso
Dec 24, 2017·Nature Communications·Florie BertrandBruno Ségui
Feb 27, 2018·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jacob M RiccaDmitriy Zamarin
Mar 27, 2018·Cytokine & Growth Factor Reviews·J F de GraafB G van den Hoogen
Aug 30, 2016·Nature Reviews. Drug Discovery·Howard L KaufmanAndrew Zloza
May 28, 2019·Life Science Alliance·Bonnie L BullockRaphael A Nemenoff
Aug 11, 2019·Journal for Immunotherapy of Cancer·Suzanne ThomasRobert S Coffin
Oct 2, 2019·Molecular Therapy : the Journal of the American Society of Gene Therapy·Keri A StrebyTimothy P Cripe

❮ Previous
Next ❯

Citations

Jan 10, 2021·International Journal of Molecular Sciences·Guendalina FroechlichNicola Zambrano
Aug 11, 2021·Viruses·Chase KangasBin He

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
enzyme-linked immunosorbent assay
transgenic
biopsies
chemical modifications
dissecting

Software Mentioned

DIVA
Prism

Related Concepts

Related Feeds

Cancer Vaccines

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