Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics
Roland E Kontermann, Guy Ungerechts, Dirk M Nettelbeck
Cancer therapeutics approved for clinical application include oncolytic viruses and antibodies, which evolved by nature, but were improved by molecular engineering. Both facilitate outstanding tumor selectivity and pleiotropic activities, but also face challenges, such as tumor heterogeneity and limited tumor penetration. An innovative strategy to address these challenges combines both agents in a single, multitasking therapeutic, i.e., an oncolytic virus engineered to express therapeutic antibodies. Such viro-antibody therapies genetically deliver antibodies to tumors from amplified virus genomes, thereby complementing viral oncolysis with antibody-defined therapeutic action. Here, we review the strategies of viro-antibody therapy that have been pursued exploiting diverse virus platforms, antibody formats, and antibody-mediated modes of action. We provide a comprehensive overview of reported antibody-encoding oncolytic viruses and highlight the achievements of 13 years of viro-antibody research. It has been shown that functional therapeutic antibodies of different formats can be expressed in and released from cancer cells infected with different oncolytic viruses. Virus-encoded antibodies have implemented direct tumor cell killing, anti-angiogenesis, or activation of adaptive immune responses to kill tumor cells, tumor stroma cells or inhibitory immune cells. Importantly, numerous reports have shown therapeutic activity complementary to viral oncolysis for these modalities. Also, challenges for future research have been revealed. Established engineering technologies for both oncolytic viruses and antibodies will enable researchers to address these challenges, facilitating the development of effective viro-antibody therapeutics.