For clinicians

About OncoVEXGM-CSF

OncoVEXGM-CSF is a 2nd generation oncolytic herpes simplex type 1 virus, encoding human GM-CSF. OncoVEXGM-CSF represents an improvement over previous vaccine and virus-based approaches for the treatment of cancer, as the virus has been genetically reprogrammed to attack cancerous cells, while healthy cells remain undamaged (Figure 2).  Primary viral infection of melanoma cells followed by virus replication and further infection and replication by progeny virons result in robust tumor cell lysis.

Figure 2: Viral Oncolysis

While OncoVEXGM-CSF is administered locally by intra-tumoral injection, it provides systemic benefit by the induction of a potent anti-tumor immune response (Figure 3). This has been demonstrated to result in the eradication of distant disease. OncoVEXGM-CSF also appears to prevent the appearance of new lesions through this systemic effect. Thus, while OncoVEXGM-CSF is locally administered, it provides a systemic effect.

The insertion of the gene for human GM-CSF into the viral genome further enhances the antitumor response both locally and at sites distant to the where the drug is injected.  Expression of GM-CSF in the local tumor environment serves to achieve several biologic goals: (a) induces local inflammation, (b) enhances dendritic cell activity, (c) is anti-angiogenic, and (d) increases HLA class II expression. Most germane to the anticancer use of GM-CSF is its mediation of dendritic cell function (Figure 4). GM-CSF is the principal mediator of proliferation, maturation, and migration of dendritic cells. These are the most potent antigen presenting cells of the immune system.

Dendritic cells display antigens on their surface in conjunction with class II major histocompatibility complex (MHC-II). Once presented, the antigen can be recognized by helper CD4+ T cells, which provide support for the development of B cells and cytotoxic CD8+ T cells (killer T cells) (Figure 4). In experiments studying tumor vaccines, GM-CSF is the most potent of a number of cytokines, adhesion molecules and other immunostimulatory molecules for the induction of specific and long-lasting antitumor immunity. By augmenting antigen presentation to lymphocytes by dendritic cells, GM-CSF stimulates T-cell mediated immune responses, providing the basis for its potential as a systemic anticancer therapy.