Gamma-irradiated Newcastle disease virus: an alternative inactivated oncolytic virotherapy

Newcastle disease virus (NDV) has been investigated as an oncolytic virus in many clinical trials, demonstrating the ability of NDV to treat a range of different cancers. However, research with NDV is hindered by biosecurity risks associated with live NDV. In addition, NDV is an important poultry pathogen that is associated with widespread livestock losses and a large economic burden. While live and chemically inactivated NDV vaccines are available, they have limited efficacy and there is a need for alternative vaccines. In this study, we inactivated NDV using γ-irradiation and tested the structural integrity, immunogenicity, and oncolytic activity of γ-NDV using in vitro and in vivo models. Our data illustrate that the overall virion structure and protein function of γ-NDV are well maintained. However, we did not detect neutralizing antibody responses after intramuscular or subcutaneous γ-NDV administration in mice. While these data do not directly support the use of γ-NDV as a vaccine candidate, our data show that γ-NDV retained its ability to kill a range of different cancer cells in vitro, suggesting γ-NDV may be a potential cancer therapeutic agent. To test this, γ-NDV was trialed as an oncolytic therapy in a murine melanoma model. This revealed that γ-NDV administration outperformed live NDV in terms of reduced tumor growth and overall survival. While further investigation is required to address the suitability of γ-NDV as a poultry vaccine, our data indicate that γ-irradiation may be a suitable inactivation method for the development of a highly effective inactivated oncolytic virotherapy.