Abstract
Oncolytic viruses (OVs) replicate selectively in tumor cells and exert anti-tumor cytotoxic activity. Among them, Newcastle Disease Virus (NDV), a bird RNA virus of the paramyxovirus family, appears outstanding. Its anti-tumor effect is based on: (i) oncolytic activity and (ii) immunostimulation. Together these activities facilitate the induction of post-oncolytic adaptive immunity. We will present milestones during the last 60 years of clinical evaluation of this virus. Two main strategies of clinical application were followed using the virus (i) as a virotherapeutic agent, which is applied systemically or (ii) as an immunostimulatory agent combined with tumor cells for vaccination of cancer patients. More recently, a third strategy evolved. It combines the strategies (i) and (ii) and includes also dendritic cells (DCs). The first step involves systemic application of NDV to condition the patient. The second step involves intradermal application of a special DC vaccine pulsed with viral oncolysate. This strategy, called NDV/DC, combines anti-cancer activity (oncolytic virotherapy) and immune-stimulatory properties (oncolytic immunotherapy) with the high potential of DCs (DC therapy) to prime naive T cells. The aim of such treatment is to first prepare the cancer-bearing host for immunocompetence and then to instruct the patient’s immune system with information about tumor-associated antigens (TAAs) of its own tumor together with danger signals derived from virus infection. This multimodal concept should optimize the generation of strong polyclonal T cell reactivity targeted against the patient’s TAAs and lead to the establishment of a long-lasting memory T cell repertoire.
Highlights
The resistance of cancers to conventional therapies necessitates the search for new treatment strategies
Integral to the live cycle of all RNA viruses is the formation of double-stranded RNA, which activates a spectrum of cellular defence mechanisms involving interferon (IFN)-Į DQG -ȕ
The results suggest either the direct involvement of the tumor cells of the vaccine in antigen presentation or the importance of prolonged expression and release of tumor-associated antigens (TAAs) with danger signals derived from viral infection of the tumor cells
Summary
The resistance of cancers to conventional therapies necessitates the search for new treatment strategies. The clinical evaluation of this virus over several decades as anticancer reagent in various clinical settings corroborates its safety and effectivity. This is based on its tumor selective replication and oncolytic activities, allowing the virus to selectively attack tumor cells while leaving healthy cells undamaged. Another aspect that has received increasing interest is the property of NDV to activate host anti-tumor immunity. We will highlight the evolution over the last 60 years of therapies based on NDV and present the latest development in this field
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