Pexastimogene devacirepvec
JX-594 is an oncolytic virus is designed to target and destroy cancer cells. It is also known as Pexa-Vec, INN pexastimogene devacirepvec) 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 strain (or Wyeth strain) 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. The virus also has the "LacZ" gene insertion under control of the p7.5 promoter. The virus kills the infected/cancer cells by lysis and also expresses GM-CSF which may help initiate an anti-tumour immune response. It has orphan drug designation from US Food and Drug Administration and EUMA for the treatment of hepatocellular carcinoma (liver cancer). In clinical trials doses have been administered by intratumoral or intravenous injection. Technology. Pexa-Vec (JX-594) is the most advanced product candidate from SillaJen's proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform. SOLVE is used to optimize virus targeting  to specific cancer types, to select transgenes to include into the viral genome, and to optimize viral infection and/or replication selectively through targeted mutations. Oncolytic viruses could have 3-prolonged attack on cancer: direct cell lysis with replication and spread, immune activation, and antivascular JX-900 (VVDD): VVDD Platform: Next-gen enhanced oncolytic immunotherapy. Clinical trials. A phase 3 randomized, open-label, clinical trial of Pexa-Vec plus sorafenib versus sorafenib is being conducted on patients with advanced hepatocellular carcinoma who have not previously received any systemic therapy. The study is being done to determine and compare overall survival for patients  in the two treatment arms. The study is Sponsored by SillaJen, Inc. Mechanism of Action of Pexa-Vec (Jx-594). The experimental therapy, Pexa-Vec, is an Attenuated vaccine|attenuated vaccinia virus engineered to stimulate anti-tumor immunity and directly lyse tumor cells. Pexa-Vec has cancer selectivity through the deactivation of its thymidine kinase gene, and it has been engineered to express the granulocyte-macrophage colony-stimulating factor gene to stimulate a systemic anti-tumor immune response. Researchers believe that Pexa-Vec may be a systemic treatment of heptocellular carcinoma by inducing tumor necrosis and shrinkage of both injected and non -injected tumors after direct intratumoral delivery. Final data from a randomized dose-ranging phase 2 study of Pexa-Vec in mainly sorafenib naïve patients with advanced hepatocellular carcinoma demonstrated that the risk of death for patients who received Pexa-Vec at the high dose was markedly reduced (by nearly 60 percent; hazard ratio = 0.41) when compared to patients randomized to a low dose control (one-tenth of the high dose). The median overall survival for high and low dose groups was 14.1 months versus 6.7 months, respectively (p = 0.020 for superiority of the high dose). Pexa-Vec was  well tolerated, with patients experiencing transient Influenza|flu -like symptoms that generally resolved within 24 hours. Study Design. Participants will be randomly assigned to one of two treatment arms, having an equal chance of receiving either Pexa-Vec followed by sorafenib, or sorafenib alone. Pipeline candidates. JX-Next Generation. Novel oncolytic viruses in SillaJen pipeline are engineered through the Selective Oncolytic Vaccinia Engineering (SOLVE) platform. JX-929. JX-929 is derived from Western Reserve strain vaccinia virus. JX-929's tumor selectivity has been optimized through deletion of thymidine kinase and vaccinia growth factor. JX-929 has been administered as a monotherapy to patients with  Breast cancer|breast , Colorectal cancer|colorectal , and pancreatic cancer via intratumoral & intravenous injections in a Phase 1, dose escalation clinical trial. This Phase 1 study showed delivery to and replication within tumors both IT and IV. JX-970. JX-970 is also derived from a Western Reserve strain Vaccinia|vaccinia virus and utilizes the same tumor selectivity mechanisms as JX-929. In addition, it expresses granulocyte-macrophage colony-stimulating factor to stimulate immune responses. In nonclinical studies, the JX-970 backbone exerted a tumor debulking effect and at the same time demonstrated a selective preference for tumor tissues. The precursor of JX-970 is JX-963 which demonstrated efficacy  in pre-clinical studies. External links. Category:Experimental cancer treatments Category:Virotherapy