Pexastimogene devacirepvec
JX-594 is an oncolytic virus (also known as Pexa-Vec,[1] INN pexastimogene devacirepvec[2]) originally constructed in Dr. Edmund Lattime's lab at Thomas Jefferson University and tested in clinical trials in melanoma patients; later licensed and further developed by SillaJen, Inc. Pexa-Vec is designed to target and destroy cancer cells.[3]
JX-594 is a modified Copenhagen[4] strain (or Wyeth strain[2]) 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.[2] 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 FDA and EUMA for the treatment of hepatocellular carcinoma (HCC).[1]
In clinical trials doses have been administered by intratumoral or intravenous injection.[2]
References
- ^ a b Jennerex Granted FDA Orphan Drug Designation for Pexa-Vec in Hepatocellular Carcinoma (HCC)
- ^ a b c d Phase 1 Study of Intratumoral Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients
- ^ Un virus contre le cancer 25 March 2012, Radio Canada Template:Fr
- ^ Transgene Presents Data on Improved Cytotoxic Activity of Oncolytic Viruses Expressing Intrabodies in Resistant Tumor Cell Lines. Oct 2016
- ^ Bos, JL (Sep 1, 1989). "ras oncogenes in human cancer: a review". Cancer Research. 49 (17): 4682–9. PMID 2547513.
- ^ "NCI Drug Dictionary". National Cancer Institute. Retrieved 25 March 2013.
- ^ "Novel Cancer-Targeting Virus Therapy Shows Efficacy in Early-Stage Trial". 31 August 2011.
- ^ Breitbach at al. (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". 477 (7362): 99–102. doi:10.1038/nature10358. PMID 21886163.
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