T Cell-Redirecting Strategies to ‘STAb’ Tumors: Beyond CARs and Bispecific Antibodies

The redirection of T cell activity towards cancer cells via targeting of tumor-associated antigens (TAAs) by soluble bispecific antibodies (bsAbs) or membrane-anchored chimeric antigen receptors is one of the most promising cancer immunotherapy strategies currently in development. We review here an emerging approach that combines aspects of antibody- and cell-based therapies: STAb immunotherapy, based on the endogenous secretion of T cell-redirecting bsAbs (STAb). STAb immunotherapies use ex vivo or in vivo genetic modifications of different cell types with nucleic acids or viral vectors encoding bsAbs; these can result in effective and persistent concentrations of antibodies. After introducing core concepts, we discuss plausible ways by which STAb strategies might be further developed to improve their potential efficacy and safety in preclinical and clinical testing.