Oncolysis by paramyxoviruses: multiple mechanisms contribute to therapeutic efficiency

Abstract

Oncolytic paramyxoviruses include some strains of Measles, Mumps, Newcastle disease, and Sendai viruses. All these viruses are well equipped for promoting highly specific and efficient malignant cell death, which can be direct and/or immuno-mediated. A number of proteins that serve as natural receptors for oncolytic paramyxoviruses are frequently overexpressed in malignant cells. Therefore, the preferential interaction of paramyxoviruses with malignant cells rather than with normal cells is promoted. Due to specific genetic defects of cancer cells in the interferon (IFN) and apoptotic pathways, viral replication has the potential to be promoted specifically in tumors. Viral mediation of syncytium formation (a polykaryonic structure) promotes intratumoral paramyxovirus replication and spreading, without exposure to host neutralizing antibodies. So, two related processes: efficient intratumoral infection spread as well as the consequent mass malignant cell death, both are enhanced. In general, the paramyxoviruses elicit strong anticancer innate and adaptive immune responses by triggering multiple danger signals. The paramyxoviruses are powerful inducers of IFN and other immuno-stimulating cytokines. These viruses efficiently promote anticancer activity of natural killer cells, dendritic cells, and cytotoxic T lymphocytes. Moreover, a neuraminidase (sialidase), a component of the viral envelope of Newcastle Disease, Mumps, and Sendai viruses, can cleave sialic acids on the surface of malignant cells thereby unmasking cancer antigens and exposing them to the immune system. These multiple mechanisms contribute to therapeutic efficacy of oncolytic paramyxoviruses and are responsible for encouraging results in preclinical and clinical studies.