Oncolytic Newcastle disease virus as a prospective anti-cancer therapy. A biologic agent with potential to break therapy resistance.

INTRODUCTION: Oncolytic viruses (OVs) selectively replicate in tumor cells and cause cancer cell death. Most OVs in clinical studies are genetically engineered. In contrast, the avian Newcastle disease virus (NDV) is a naturally oncolytic RNA virus. While anti-viral immunity is considered a major problem in achieving maximal tumor cell killing by OVs, this review discusses the importance of NDV immunogenic cell death (ICD) and how anti-viral immune responses can be integrated to induce maximal post-oncolytic T-cell-mediated anti-tumor immunity. Since replication of NDV is independent of host cell DNA replication (which is the target of many cytostatic drugs and radiotherapy) and because of other findings, oncolytic NDV is a candidate agent to break therapy resistance of tumor cells. AREAS COVERED: Properties of this avian paramyxovirus are summarized with special emphasis to its anti-neoplastic and immune-stimulatory properties. The review then discusses prospective anti-cancer therapies, including treatments with NDV alone, and combinations with an autologous NDV-modified tumor cell vaccine or with a viral oncolysate pulsed dendritic cell vaccine. Various combinatorial approaches between these and with other modalities are also reviewed. EXPERT OPINION: Post-oncolytic anti-tumor immunity based on ICD is in the expert's opinion of greater importance for long-term therapeutic effects than maximal tumor cell killing. Of the various combinatorial approaches discussed, the most promising and feasible for clinical practice appears to be the combination of systemic NDV pre-treatment with anti-tumor vaccination.