A new study published in Molecular Therapy shows that JX-594, a first-in-class targeted oncolytic virus products for cancer being developed by Jennerex, Inc selectively targets and kills a broad range of cancer cells.
The study demonstrated that JX-594’s cancer-selectivity was multi-mechanistic and dependent on the biological traits common to cancer cells that allow them to rapidly expand and avoid destruction by the immune system. Specifically, replication of JX-594 was activated by epidermal growth factor receptor (EGFR)/Ras pathway signaling, cellular thymidine kinase (TK) levels, and cancer cell resistance to type I interferons (IFNs).
JX-594 was tested in multiple models, including human tumor tissue and normal tissue from surgical samples. The journal article written by authors Kelley A. Parato, Ph.D., of Ontario Hospital Research Institute’s Centre for Innovative Cancer Research and Caroline J. Breitbach, Ph.D., director, clinical & translational research, of Jennerex was published in January in the online edition of Molecular Therapy, the official journal of The American Society of Gene & Cell Therapy.
Strong clinical data
“We believe that this study clearly explains how JX-594 is able to specifically target and destroy cancer cells in patients while leaving the surrounding healthy cells intact. This has translated into strong clinical data for JX-594, including tumor destruction and a favorable safety profile in Phase 2 clinical trials,” said David H. Kirn, M.D., president and chief medical officer of Jennerex. “Importantly, these data confirm that JX-594 has a large therapeutic index that is driven by the common genetic traits present in the vast majority of patients’ cancers, including colorectal, lung, liver and others.”
JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. JX-594 is designed to attack cancer through three diverse mechanisms of action: 1) the lysis of cancer cells through viral replication, 2) the shutdown of the blood supply to tumors through vascular targeting and destruction, and 3) the stimulation of the body’s immune response against cancer cells, i.e., active immunotherapy. Phase I and Phase II clinical trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients (over 120 treated to date). Objective tumor responses have been demonstrated in a variety of cancers including liver, colon, kidney, lung cancer and melanoma. JX-594 has had a favorable safety profile to date with predictable and generally mild side effects that typically include flu-like symptoms that resolve in 24 to 48 hours.
JX-594 is the most advanced product candidate from Jennerex’s proprietary SOLVE? (Selective Oncolytic Vaccinia Engineering) platform. SOLVE takes advantage of the natural attributes of poxviruses as well as their ability to be genetically engineered to produce safe, therapeutic viruses that can infect solid tumors both systemically and locally. The vaccinia poxvirus strain backbone of JX-594 has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells. JX-594 was engineered to enhance this natural safety and cancer-selectivity by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. To enhance product efficacy, JX-594 is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack.
For more information:
Parato KA, Breitbach CJ, Le Boeuf F, Wang J, Storbeck C, Ilkow C, et al.
The Oncolytic Poxvirus JX-594 Selectively Replicates in and Destroys Cancer CellsDriven by Genetic Pathways Commonly Activated in Cancers. Molecular Therapy (2011); doi:10.1038/mt.2011.276