abstract |
The present invention discloses a recombinant vaccinia virus (VV) virion that is resistant to antiviral defense and has enhanced anti-tumor activity. In one embodiment, the recombinant VV comprises one or more variant VV proteins having a mutation in one or more neutralizing antibody epitopes, thereby providing virus evasion from the neutralizing antibody. In another embodiment, the recombinant VV is resistant to complement-mediated neutralization due to expression of a modulator of complement activation (eg, CD55). In another embodiment, the recombinant VV has enhanced anti-tumor activity due to expression of a bispecific antibody that co-targets cancer cells and immune effector cells, or expression of a polypeptide that blocks the PD-1 pathway. Recombinant vaccinia virus virions can be used to treat cancer in a subject. |