Fig. 1

BiTE-encoding oncolytic viruses for cancer immunotherapy. Oncolytic viruses (OVs) selectively infect tumor cells, followed by lytic replication (1). In addition to direct tumor debulking, viral oncolysis triggers the release of danger- and pathogen-associated molecular patterns, cytokines, chemokines, and tumor-associated antigens (2). Upon immunogenic tumor cell death (ICD), local inflammation as well as innate and adaptive anti-tumor immune responses can set the stage for effective immunotherapy. Bispecific T cell engagers (BiTEs) redirect T cells to tumor cell surface antigens. OVs can be engineered for tumor-directed BiTE expression to benefit from high BiTE concentrations at the inflamed tumor site, while avoiding systemic toxicities (3). Preclinical studies have shown efficacy of this approach, utilizing BiTE-encoding OVs to engage endogenous or adoptively transferred T cells, including genetically modified CAR T cells (3a). Aside from direct tumor cell targeting, OV-BiTEs can also be used effectively to target immunosuppressive cells of the tumor microenvironment such as cancer-associated fibroblasts (3b) and tumor-associated macrophages (3c). Created with BioRender.com