Targeted and Armed Oncolytic Poxviruses for Cancer: the Lead Example of JX-594
Caroline J. Breitbach, Steve H. Thorne, John C. Bell and David H. Kirn
Affiliation: Jennerex Inc. San Francisco, CA, USA.
Oncolytic viruses (OVs) are designed to replicate in, and subsequently lyse cancer cells. Numerous oncolytic
virus platforms are currently in development. Here we review preclinical and clinical experience with JX-594, the lead
candidate from the targeted and armed oncolytic poxvirus class. JX-594 is derived from a vaccinia vaccine strain that has
been engineered for 1) enhanced cancer targeting and 2) has been “armed” with the therapeutic transgene granulocytemacrophage
colony stimulating factor (GM-CSF) to stimulate anti-tumoral immunity. Poxviruses have many ideal features
for use as oncolytic agents. The development of oncolytic vaccinia viruses is supported by a large safety database
accumulated in the smallpox eradication program. In addition, poxviruses have evolved unique capabilities for systemic
spread through the blood that can be harnessed for the treatment of metastatic disease. JX-594 demonstrates a high degree
of cancer selectivity and systemic efficacy by multiple mechanisms-of-action (MOAs) in preclinical testing. Data from
Phase 1 and 2 clinical trials has confirmed that these features result in potent and systemic efficacy in patients with treatment
refractory metastatic cancers.
Keywords: Oncolytic poxvirus, JX-594, Cancer, Oncolytic viruses, vaccinia vaccine strain, granulocytemacrophage colony stimulating factor (GM-CSF), metastatic disease, multiple mechanisms-of-action (MOAs)
Rights & PermissionsPrintExport