JX594

JX-594, also known as Pexa-Vec, is an oncolytic vaccinia virus developed for cancer therapy. It is genetically modified to selectively replicate in cancer cells and to stimulate an anti-tumor immune response.

Mechanism and design

The virus is engineered to delete its thymidine kinase gene, which restricts replication to rapidly dividing cells such as tumor cells, reducing infection of normal tissues. In addition, JX-594 carries a transgene encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), intended to recruit and activate dendritic cells at the tumor site and enhance systemic anti-tumor immunity. The combination aims to cause direct oncolysis while promoting immune recognition of tumor-associated antigens.

Delivery and activity

JX-594 is typically delivered by intratumoral injection, though systemic administration has been explored. Upon replication and lysis of infected tumor cells, tumor antigens are released and presented to the immune system, with GM-CSF further stimulating immune activation. This approach seeks both local tumor destruction and broader immune-mediated control of cancer.

Clinical development

JX-594 progressed through early-phase clinical trials to evaluate safety, dosing, and preliminary efficacy in several solid tumors, including hepatocellular carcinoma. Results indicated a manageable safety profile and some evidence of tumor responses and immune activation. The therapy was studied as a monotherapy and in combination with other cancer treatments.

Regulatory status

As of the mid-2010s, JX-594 did not achieve regulatory approval for hepatocellular carcinoma or other cancers in major markets, with Phase III results in hepatocellular carcinoma not meeting predefined endpoints. Development plans shifted, and the program underwent corporate changes.

See also

Oncolytic virus therapy; vaccinia virus in cancer treatment; GM-CSF in cancer immunotherapy.