Beyond safety: suicide systems in cell-based cancer therapies.

Abstract

Cell-based therapies are promising for treating solid tumors, but challenges like tumor heterogeneity, antigen escape, and immunosuppressive microenvironments hinder their efficacy. Inducible suicide gene systems, often viewed solely as safety mechanisms, offer an underappreciated opportunity to enhance cellular therapies. These systems, triggered by various mechanisms (prodrugs, ligands, antibodies, or small molecules), enable controlled elimination of therapeutic cells. Recent developments demonstrate that this controlled cell death, especially when inducing immunogenic cell death (ICD), can kill even resistant tumor cells and reshape the tumor microenvironment (TME) from suppressive to stimulatory. This review highlights the transformative potential of integrating these suicide systems into cell therapies, overcoming key limitations, and amplifying antitumor responses while ensuring safety.