Tumor cells expressing GM-CSF and thymidine kinase–dependent viral replication machinery (Pexa-Vec target)

Tumor cells expressing GM-CSF and thymidine kinase–dependent viral replication machinery refers to a specific cellular state targeted by oncolytic immunotherapy, most notably Pexastimogene devacirepvec (Pexa-Vec or JX-594). This therapeutic strategy utilizes a modified vaccinia virus with a deleted thymidine kinase (TK) gene, which restricts viral replication to cells with high endogenous TK levels, a common feature of malignant cells (Heo et al., 2013, Nature Medicine). The virus is also engineered to express human granulocyte-macrophage colony-stimulating factor (GM-CSF) within the infected tumor cells. The biological function of this target system involves direct oncolysis through viral replication and the subsequent induction of a systemic anti-tumor immune response (Breitbach et al., 2011, Nature). By expressing GM-CSF, the infected cells recruit and activate antigen-presenting cells to the tumor microenvironment, promoting the recognition of tumor-associated antigens. This target is primarily utilized in the treatment of advanced solid tumors, such as hepatocellular carcinoma, where it aims to turn "cold" tumors "hot" by stimulating immune infiltration. Safety concerns include transient flu-like symptoms, potential for viral shedding, and the development of neutralizing antibodies that may limit repeat dosing efficacy (NCI Drug Dictionary).

Other names

Pexa-Vec targetJX-594 targetGM-CSF-expressing oncolytic vaccinia targetTK-dependent oncolytic virus target

Selective oncolytic viral replication in thymidine kinase-high cells and GM-CSF-mediated immune activation