Oncolytic herpes virus

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Further information: Oncolytic virus
Oncolytic herpes virus
TEM micrograph of a herpes simplex virus.
Virus classification Edit this classification
(unranked): Virus
Realm: Duplodnaviria
Kingdom:
Heunggongvirae
Phylum: Peploviricota
Class: Herviviricetes
Order: Herpesvirales
Family:
Orthoherpesviridae
Genus: Simplexvirus
Species:
Human alphaherpesvirus 1

Many variants of

ICP34.5, ICP6/UL39, and ICP47
.

Electron Micrograph of herpes virus

HSV1716

HSV1716 is a first generation

ICP34.5. ICP34.5 is a neurovirulence gene (enabling the virus to replicate in neurons of the brain and spinal cord). Deletion of this gene provides the property of tumor-selective replication to the virus (i.e. largely prevents replication in normal cells, while still allowing replication in tumor cells), although it also reduces replication in tumor cells as compared to wild type HSV.[2][3]

A vital part of the normal mechanism of HSV-1, the ICP34.5 protein has been proposed to condition

cell lines in tissue culture
.

An HSV1716 variant, HSV1716NTR is an oncolytic virus generated by inserting the enzyme

noradrenaline transporter to deliver radioactive iodine into individual infected cancer cells, by tagging a protein that cancer cells transport. The nor-adrenaline transporter specifically transports a compound containing radioactive iodine across the cell membrane, using genes from the virus. The only cells in the body that receive a significant radiation dose are those infected and their immediate neighbours.[5]

Clinical trials

G207

G207 was constructed as a second-generation vector from HSV-1 laboratory strain F, with ICP34.5 deleted and the ICP6 gene inactivated by insertion of the E. coli

LacZ gene.[12]

Two phase I clinical trials in glioma were completed.[13][14][15] The results of the first trial were published simultaneously with the first trial of HSV1716 in 2000, with commentators praising the demonstration of safety of these viruses when injected into brain tumours but also expressing disappointment that viral replication could not be demonstrated due to the difficulty of taking biopsies from brain tumours.[16]

NV1020

NV1020 is an oncolytic herpes virus initially developed by Medigene Inc. and licensed for development by Catherex Inc. in 2010.

peritoneal cancer showed that NV1020 is more effective at lower doses.[18]

Clinical trials

A Phase I/II study completed in 2008 evaluating NV1020 for treatment of metastatic

FDG-PET scans, showing 67% of patients had an initial increase in tumour size then followed by a decrease in 64% of patients.[20][18]

Talimogene laherparepvec

Main article: Talimogene laherparepvec

Talimogene laherparepvec is the USAN name for the oncolytic virus also known as 'OncoVEX GM-CSF'. It was developed by BioVex Inc. (Woburn, MA, USA & Oxford, UK) until BioVex was purchased by Amgen in January 2011.[21]

It is a second-generation

GM-CSF, an immune stimulatory cytokine.[2][3]
Deletion of the gene encoding ICP47 also puts the US11 gene (a late gene) under control of the immediate early ICP47 promoter. The earlier and greater expression of US11 (also involved in overcoming PKR-mediated responses) largely overcomes the reduction in replication in tumor cells of ICP34.5-deleted HSV as compared to wild type virus, but without reducing tumor selectivity.

Clinical trials

Including phase III : See Talimogene laherparepvec

See also

References

  1. ^
    PMID 12522436
    .
  2. ^
    PMID 8887567
    .
  3. ^
    S2CID 11464646
    .
  4. PMID 19528476
    .
  5. PMID 22414636
    .
  6. S2CID 14604628
    .
  7. PMID 11960316
    .
  8. S2CID 43914133
    .
  9. S2CID 34442464
    .
  10. ^ Clinical trial number NCT01721018 for "Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma" at ClinicalTrials.gov
  11. ^ Clinical trial number NCT00931931 for "HSV1716 in Patients With Non-Central Nervous System (Non-CNS) Solid Tumors" at ClinicalTrials.gov
  12. S2CID 8712053
    .
  13. PMID 10845725
    .
  14. ^ Clinical trial number NCT00028158 for "Safety and Effectiveness Study of G207, a Tumor-Killing Virus, in Patients With Recurrent Brain Cancer" at ClinicalTrials.gov
  15. ^ Clinical trial number NCT00157703 for "G207 Followed by Radiation Therapy in Malignant Glioma" at ClinicalTrials.gov
  16. PMID 10845717
    .
  17. ^ "MediGene AG divests Oncolytic Herpes Simplex Viruses (oHSV) program to Catherex, Inc" (Press release). MediGene AG. April 13, 2010. Archived from the original on October 29, 2013. Retrieved May 7, 2013.
  18. ^
    PMID 20486770
    .
  19. ^ Clinical trial number NCT00149396 for "Safety and Efficacy of a Genetically Engineered Herpes Simplex Virus NV1020 to Treat Colorectal Cancer Metastatic to Liver" at ClinicalTrials.gov
  20. PMID 21895536
    .
  21. ^ "Amgen, Form 8-K, Current Report, Filing Date Jan 26, 2012" (PDF). secdatabase.com. Retrieved Jan 8, 2013.
  22. ^ "OncoVEXGM-CSF RAC Submission" (PDF). NIH Genetic Modification Clinical Research Information System (GeMCRIS®). Archived from the original (PDF) on 28 May 2010. Retrieved 1 April 2013.
  23. S2CID 30005391
    .
  24. PMID 22116674
    .
  25. S2CID 11220164
    .

External links
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