The objectives of current study were to ascertain whether in vitro human cancer cell lines expressing nectin4 were susceptible to and killed by a nectin4-retargeted onco-immunotherapeutic herpesvirus (nectin4-ReHV), whether susceptibility was influenced by the extent of nectin4 expression, to develop immunocompetent murine models of human nectin4-positive cancers, and to evaluate mono- and combination therapy and long-term anticancer vaccination. Here, NECTIN4 is linked to cancer.