Provided herein are recombinant poxviruses comprising heterologous or native nucleic acids specifying excess double-stranded RNA (dsRNA) early in infection, which may further comprise heterologous nucleic acids encoding one or more costimulatory molecules, and/or heterologous nucleic acids encoding one or more infectious disease-associated antigens or tumor-associated antigens, as well as pharmaceutical compositions comprising such recombinant poxviruses and methods and uses thereof. The recombinant poxviruses provided herein enhance innate and adaptive immune activation in subjects compared to identical recombinant poxviruses lacking heterologous or native transcription units specifying excess early dsRNA.

The disclosure provides Myxoma viruses that express one or more multi-specific immune cell engagers, such as BiKE, BiTE and/or MiTE and their use in inhibiting and/or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more multi-specific immune cell engagers, and the use of the leukocyte for inhibiting and/or treating a hematological cancer in a subject.

Myxoma viruses that are deficient in the activity of a Myxoma virus protein selected from the group consisting of M11L, M063, M 136, M-T4 and M-T7 are useful for treating cancer.