A Recombinant Antibody-Expressing Influenza Virus Delays Tumor Growth in a Mouse Model

Influenza A virus (IAV) has shown promise as an oncolytic agent. To improve IAV as an oncolytic virus, we sought to design a transgenic virus expressing an immune checkpoint-inhibiting antibody during the viral life cycle. To test whether it was possible to express an antibody during infection, an influenza virus was constructed encoding the heavy chain of an antibody on the PB1 segment and the light chain of an antibody on the PA segment. This antibody-expressing IAV grows to high titers, and the antibodies secreted from infected cells exhibit comparable functionality with hybridoma-produced antibodies. To enhance the anti-cancer activity of IAV, an influenza virus was engineered to express a single-chain antibody antagonizing the immune checkpoint CTLA4 (IAV-CTLA4). In mice implanted with the aggressive B16-F10 melanoma, intratumoral injection with IAV-CTLA4 delayed the growth of treated tumors, mediated an abscopal effect, and increased overall survival.