Two of the most exciting new areas of cancer therapy are the use of oncolytic viruses and immune-stimulating monoclonal antibodies. Each approach has shown great promise in animal models and some successes in early clinical trials, but there remain significant barriers to highly effective therapy. To date, the two technologies have been developed independently of each other, for the most part. However, in this issue of Molecular Therapy, Yu et al.1 describe experiments that combine the strengths of both approaches by creating an oncolytic vaccinia virus (VV) that has the ability to home to tumors where it can replicate and induce tumor lysis but also has the ability to secrete a bispecific T-cell engager (BiTE) that can bind T cells to tumor cells and additionally induce immune-mediated tumor cell destruction (Figure 1).