Pexastimogene devacirepvec

JX-594 is an oncolytic virus is designed to target and destroy cancer cells.[1] It is also known as Pexa-Vec,[2] INN pexastimogene devacirepvec[3]) and was constructed in Dr. Edmund Lattime's lab at Thomas Jefferson University, tested in clinical trials on melanoma patients, and licensed and further developed by SillaJen.

JX-594 is a modified Copenhagen[4] strain (or Wyeth strain[3]) vaccinia poxvirus engineered by addition of the GM-CSF gene and deletion of the thymidine kinase gene which limits viral replication to cells with high levels of thymidine kinase, typically seen in cancer cells with a mutated RAS or p53 gene.[5] The virus also has the LacZ gene insertion under control of the p7.5 promoter.[3] The virus kills the infected/cancer cells by lysis and also expresses GM-CSF which may help initiate an anti-tumour immune response.[6][7] [8]

It has orphan drug designation from US Food and Drug Administration and EUMA[clarification needed] for the treatment of hepatocellular carcinoma (liver cancer).[2]

In clinical trials doses have been administered by intratumoral or intravenous injection.[3]

  1. ^ Un virus contre le cancer 25 March 2012, Radio Canada (in French)
  2. ^ a b Jennerex Granted FDA Orphan Drug Designation for Pexa-Vec in Hepatocellular Carcinoma (HCC)
  3. ^ a b c d Phase 1 Study of Intratumoral Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients
  4. ^ Transgene Presents Data on Improved Cytotoxic Activity of Oncolytic Viruses Expressing Intrabodies in Resistant Tumor Cell Lines. October 2016
  5. ^ Bos, JL (September 1, 1989). "ras oncogenes in human cancer: a review". Cancer Research. 49 (17): 4682–9. PMID 2547513.
  6. ^ "NCI Drug Dictionary". National Cancer Institute. 2011-02-02. Retrieved 25 March 2013.
  7. ^ "Novel Cancer-Targeting Virus Therapy Shows Efficacy in Early-Stage Trial". 31 August 2011.
  8. ^ Breitbach at al. (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature. 477 (7362): 99–102. Bibcode:2011Natur.477...99B. doi:10.1038/nature10358. PMID 21886163. S2CID 4365604.