Disclosed herein, in certain embodiments, are recombinant myxoma viruses (MYXVs) and nucleic acid constructs encoding the recombinant MYXVs. In some embodiments, the MYXVs are engineered to inactivate or attenuate an activity or expression level of an M153 protein. In some embodiments, the MYXVs are engineered to express one or more transgenes such as a tumor necrosis factor (TNF), interleukin-12 (IL-12), or decorin. Also disclosed herein, in certain embodiments, are methods of using the MYXVs. Some embodiments include providing a MYXV as described herein to a subject in need thereof.

The present invention relates to a chimeric poxvirus with improved anticancer activity (higher cancer cell killing capacities and better tumor selectivity), as well as variant version thereof with one or more altered viral genes, recombinant versions thereof comprise one or more nucleic acid(s) of interest and recombinant variant versions thereof, all of which may be included in a composition and used for the treatment of a disease, in particular proliferative disease, notably cancers.