Abstract: Provided herein are clonal strains of a vaccinia virus that exhibits enhanced anti-tumor properties and/or reduced immunogenicity, and recombinant vaccinia virus derived from the same. Also provided herein are recombinant oncolytic virus strains that include an inactivating mutation in one or more viral genes, and/or one of more heterologous nucleic acids each encoding one or more heterologous gene products. The viruses, e.g., vaccinia viruses, provided herein, including recombinant vaccinia viruses, can be used as an oncolytic virus therapy, e.g., an oncolytic vaccinia virus therapy, for treating cancer. Also provided herein are pharmaceutical compositions and methods and uses of the viruses, e.g., vaccinia viruses, for treating cancer, as well as nucleic acids encoding the viruses.