This disclosure relates to modified viruses, e.g., oncolytic vaccinia viruses, which have been modified to contain an exogenous nucleic acid that codes for a variant HMGB1 protein. It provides, at least in part, that vaccinia viruses modified to contain nucleic acid encoding variant HMGB1 and that express a variant HMGB1 or a fragment thereof can achieve a synergistic effect in combination with chemotherapy. Further, this disclosure provides for oncolytic vaccinia viruses and methods of using them in the treatment of various cancers.