Oncolytic HSV as in situ Vaccine for the Treatment of Cancer

Dr. Stefan Ries

MediGene AG, Lochhamer Straße 11, D-82152 Martinsried, Germany

Replication-selective oncolytic Herpes Simplex viruses (HSV) show great promise in clinical development as agents for cancer treatment, because they selectively amplify, through replication and spread, the input dose of virus in the tumor. To date, clinical studies have demonstrated that treatment with oncolytic HSV is well tolerated, and that tumor necrosis can occur in patients.

However, in light of a clearer understanding of the complexity of solid human tumors, it seems promising to couple the lytic capability of oncolytic viruses with the capacity to deliver therapeutic factors. The immune system is a complex mixture of effector cells and proteins that have the potential to selectively recognize and eradicate cancerous tissue in the body based on differences between normal and malignant cells. Immunostimulatory molecules, such as cytokines, seem to be particular good candidates for therapeutic transgenes, as early cytokine production after viral infection of the tumor may initially recruit or stimulate immune cells in the region of the tumor. Several oncolytic HSV vectors have been engineered to encode immunostimulatory cytokines in an attempt to enhance their potential at eliciting an immune response that supports the lytic function of the virus.

In fact, the antitumor efficacy of some of these modified viruses was improved compared to the purely oncolytic virus, implying that a lower dose of virus may be used clinically to potentially improve the therapeutic index of oncolytic viral therapy. More importantly, in the neoadjuvant setting this approach may offer the possibility of protection against microscopic residual disease after surgical resection, or in radiation/chemotherapy resistant tumors.