Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy

Abstract
Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus(NDV)asabiologicalagentwithpotentialtobreaktherapyresistance. Thisavianviruscombines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11describedimmunestimulatoryproperties. FiftyyearsofclinicalapplicationofNDVgivewitnessto the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the successful production of NDV according to Good Manufacturing Practice (GMP). Based on this, IOZK in Cologne, Germany, obtained a GMP certificate for the production of a dendritic cell vaccine loadedwithtumorantigensfromalysateofpatient-derivedtumorcellstogetherwithimmunological dangersignalsfromNDVforintracutaneousapplication. Thisupdateincludessinglecasereportsand retrospective analyses from patients treated at IOZK. The review also presents future perspectives, including the concept of in situ vaccination and the combination of NDV or other oncolytic viruses with checkpoint inhibitors.
Keywords: NDV; viral oncolysis; immunogenic cell death; type I interferon; dendritic cells; active-specific immunotherapy; bispecific antibodies; gene therapy; checkpoint inhibition; T cell costimulation; RIG-I; IFNAR