Viral Anti-Inflammatory Proteins: The Potential for Immunotherapeutic Applications in Cancer

J.   A.   Davids; G.      Munuswamy - Ramunujam; L.   Y.   Liu; E.      Dai; A.      Lucas

doi:10.2174/187152308784533159

Abstract

Complex viruses such as herpes, poxvirus, HIV and influenza subvert the immune system, blocking host antiviral defenses. The innate immune inflammatory response represents the first line of defense against invading pathogens. This first line of defense also initiates cellular healing after infection or injury. With tumors, however, the innate immune response is a classic double-edged sword, with the capacity to promote or terminate tumor progression. The proliferation and invasion of many cancers as well as metastasis have now been linked with an increase in many of the molecular signals that drive inflammation. Inflammatory responses are mediated by endothelial cells in the arterial walls and by neutrophils, monocytes /macrophages and T lymphocytes in the circulating blood. Activated cells release chemokines, cytokines, serine proteases in the thrombotic and thrombolytic pathways, apoptotic serine and cysteine proteases, and growth factors that accelerate cellular proliferation, migration and invasion. We are investigating potential therapeutic applications of virus-derived immune-modulating proteins, as immunotherapeutics for use in disease states driven by excessive inflammatory responses. In this review we will describe the roles of excess inflammatory responses in cancer and discuss potential applications of viral anti-inflammatory proteins for the treatment of cancer with special emphasis on immunemodulating proteins that target chemokine and serine protease pathways. These immune-modulating proteins represent a new class of naturally occurring, virus-derived immunomodulating drugs. While the rest of this special issue will be discussing virus induced disease, here we will discuss the potential for harvesting viral immune-modulating proteins as a new class of immunotherapeutic.

Keywords: Cancer, metastasis, inflammation, innate immune, serine protease, serpin, chemokine, virus