TVEC is approved for melanoma and is based on herpes simplex virus. One challenge with development of many OVs is the requirement to inject them into the tumor directly. There is work being done in this space to allow systemic administration (eg intravenous) but the presence of virus neutralizing antibodies complicates development. Most OVs are engineered in some way to make them replicate preferentially in tumor cells since any cell (including immune and healthy cells) in the tumor microenvironment may be infected if they express entry receptors.