Replicative conditioning of Herpes simplex type 1 virus by Survivin promoter, combined to ERBB2 retargeting, improves tumour cell-restricted oncolysis.

Scientific Reports
Emanuele SassoNicola Zambrano

Abstract

Oncolytic virotherapy is emerging as a promising therapeutic option for solid tumours. Several oncolytic vectors in clinical testing are based on attenuated viruses; thus, efforts are being taken to develop a new repertoire of oncolytic viruses, based on virulent viral genomes. This possibility, however, raises concerns dealing with the safety features of the virulent phenotypes. We generated a double regulated Herpes simplex type-1 virus (HSV-1), in which tumour cell restricted replicative potential was combined to selective entry via ERBB2 receptor retargeting. The transcriptional control of the viral alpha4 gene encoding for the infected cell protein-4 (ICP4) by the cellular Survivin/BIRC5 promoter conferred a tumour cell-restricted replicative potential to a virulent HSV-1 genome. The combination of the additional ERBB2 retargeting further improved the selectivity for tumour cells, conferring to the double regulated virus a very limited ability to infect and propagate in non-cancerous cells. Accordingly, a suitable replicative and cytotoxic potential was maintained in tumour cell lines, allowing the double regulated virus to synergize in vivo with immune checkpoint (anti-PD-1) blockade in immunocompetent mice. Thus, restric...Continue Reading

References

May 23, 1998·FEBS Letters·A CaruzF Arenzana-Seisdedos
Apr 28, 2001·Neoplasia : an International Journal for Oncology Research·E HiyamaJ W Shay
Oct 9, 2002·Annals of Surgery·John T MullenKenneth K Tanabe
Jun 26, 2003·Nucleic Acids Research·Domènec FarréXavier Messeguer
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie P PiechockiWei-Zen Wei
Jul 13, 2004·Seminars in Cancer Biology·Fran Balkwill
Sep 11, 2004·Cancer Gene Therapy·Jin-Shing ChenMien-Chie Hung
May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Laura MenottiGabriella Campadelli-Fiume
Jun 30, 2009·Cancer Treatment Reviews·Bríd M RyanMichael J Duffy
Feb 25, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cleo Y F LeeWilliam W G Jia
Dec 22, 2012·The EMBO Journal·Bianca HeemskerkTon N M Schumacher
Nov 8, 2013·Molecular Biology Reports·Romain BoidotSarab Lizard-Nacol
Apr 26, 2014·Cancer Immunology Research·E Antonio Chiocca, Samuel D Rabkin
Sep 10, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lucia MazzacuratiPaola Grandi
Aug 14, 2015·Journal of Virology·David C BloomRichard Voellmy
Sep 2, 2015·Nature Reviews. Drug Discovery·Howard L KaufmanAndrew Zloza
Apr 14, 2016·Oncotarget·Zahid M DelwarWilliam W Jia
May 22, 2016·Blood·Jennifer N Brudno, James N Kochenderfer
Sep 11, 2016·Current Opinion in Virology·William F GoinsJoseph C Glorioso
Sep 15, 2016·Molecular Therapy Oncolytics·Challice L BonifantKevin J Curran
Sep 24, 2016·Journal for Immunotherapy of Cancer·Hasan RehmanHoward L Kaufman
Jan 18, 2017·Proceedings of the National Academy of Sciences of the United States of America·Kenji ChamotoTasuku Honjo
Feb 25, 2017·Nature Reviews. Cancer·Mark YarchoanElizabeth M Jaffee
Sep 29, 2017·Frontiers in Oncology·Sachin R JhawarAndrew Zloza
Jan 10, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jacob P van VlotenByram W Bridle
Feb 9, 2018·Human Vaccines & Immunotherapeutics·Robert M ConryTimothy Graham Norwood
Apr 27, 2018·Nature Reviews. Cancer·Kwame Twumasi-BoatengBrad H Nelson
Nov 15, 2018·Clinical and Translational Medicine·Christopher J LaRocca, Susanne G Warner
Dec 28, 2018·Molecular Cancer Research : MCR·Nina Marí Gual Pimenta de QueirozGlen N Barber
Feb 14, 2019·Scientific Reports·Nikolas Tim MartinMarie-Claude Bourgeois-Daigneault

❮ Previous
Next ❯

Citations

Nov 25, 2020·Expert Opinion on Drug Discovery·Shunchuan Zhang, Samuel D Rabkin
Nov 11, 2020·International Journal of Molecular Sciences·Laura Menotti, Elisa Avitabile
Jan 10, 2021·International Journal of Molecular Sciences·Guendalina FroechlichNicola Zambrano

❮ Previous
Next ❯

Datasets Mentioned

BETA
GU734771.1

Methods Mentioned

BETA
Assay
PCR
fluorescence microscopy
transgenic

Software Mentioned

GraphPad Prism
Firehose stddata
PROMO )

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.