When going viral, the right model makes all the difference

Oncolytic virotherapy has been successful in complete tumor regression in a variety of  animal model systems.  This therapeutic approach relies on lytic viruses that conditionally replicate in and kill tumor cells.  Tumor associated proteins released from lysed tumor cells activate a cytotoxic T lymphocyte (CTL) immune response, further aiding in the elimination of the tumor.

Upon viral infection in healthy cells, a type 1 interferon response is initiated preventing viral replication. However, viruses such as the Herpes simplex virus type-1 (HSV) produce proteins that inactivate this pathway, so that they can replicate in the cells they infect.  For HSV, the “infected cell protein 0” (ICP0) is responsible for suppressing the antiviral response by the cell. Interestingly, the antiviral response is typically not active in tumor cells. Therefore, removal of the ICP0 protein prevents replication of HSV in healthy cells, while still allowing replication in tumor cells. Such a modified virus should therefore be ideal for destruction of tumors.

In a new study published in Molecular Therapy, researchers present data on a previously described ICP0 null HSV mutant, KM100, identified with broad specificity for killing both murine and human tumor cells using a mouse breast cancer model.

Several important conclusions are reached in this paper.  The effectiveness of a virus to kill cultured tumor cells does not predict its ability to kill when introduced into an animal.  When testing an oncolytic virus, it is important to use the appropriate immunological animal model that reflects the local and systemic immune profile for the tumor of interest. Only then can the effectiveness of the oncolytic virus be properly gauged.