TRUCKs with IL-18 payload: Toward shaping the immune landscape for a more efficacious CAR T-cell therapy of solid cancer

Adoptive therapy with chimeric antigen receptor (CAR)-modified T cells achieved remissions of so far refractory leukemia/lymphoma; however, the treatment of solid tumors still remains challenging. This is thought to be due to the hostile conditions of the tumor stroma and the repressive immune cell infiltrate. Most recently, CAR T cells are being used as redirected “living factories” to deposit immune-modulating cytokines in the tumor tissue aiming at converting the immune cell environment into a more favorite one to sustain a productive antitumor response. IL-18 releasing CAR- or T cell receptor (TCR)-modified T cells showed superior antitumor activities in several tumor models. Such IL-18 TRUCKs or “4th generation” CAR T cells are going to change our concepts of treating tumors and delivering drugs to predefined lesions in the near future.