Herpes simplex virus oncolytic vaccine therapy in melanoma

Abstract

Importance of the field: Advanced melanoma is a devastating disease with a five year survival for Stage IV disease of 10 – 20% and a median survival of 6 – 18 months depending on sub-stage. Current FDA approved therapies demonstrate limited response rates, few complete remissions and no proven survival benefit. New therapies are clearly needed. JSI/34.5-/47-/GM-CSF is a herpes simplex virus-1 (OncoVEX^GM-CSF) oncolytic vaccine therapy designed to induce local and systemic anti-tumor immune responses.

Areas covered in this review: Evolution of current herpes simplex virus oncolytic vaccines from preclinical to clinical studies from 1994 to 2010.

What the reader will gain: Preclinical studies have shown that herpes simplex virus-1 oncolytic vaccines generate local tumor destruction through the lytic action of the virus and local and systemic immune responses. Phase I studies demonstrated limited toxicities with no neurotoxicty. Phase II studies demonstrated durable regressions in patients with metastatic melanoma. A Phase III trial in melanoma is ongoing to determine clinical effectiveness, and a Phase III trial in head and neck cancer will initiate during 2010.

Take home message: JSI/34.5-/47-/GM-CSF is a new generation herpes simplex virus-1 oncolytic vaccine that demonstrates direct tumor lysis and systemic immune responses. Early clinical studies have yielded preliminary evidence of activity.

Keywords::

• herpes simplex virus 1
• immunotherapy
• melanoma
• oncolytic vaccine