Chimeric antigen receptor (CAR) T cells have limited efficacy against solid tumors. Wagner and colleagues address this problem and show that CAR T cells targeting the EDB (extra domain B) splice variant of fibronectin, a pan-cancer solid tumor target, have potent antitumor activity in preclinical solid tumor models. EDB-targeting CAR T cells kill tumor targets in vitro and in vivo, while also inducing bystander killing and remodeling of the tumor vasculature. EDB-CAR T cells also persist long-term after treatment and protect animals against subsequent tumor challenges. The data highlight a cancer-specific splice variant that can safely be targeted. Read more in this issue on page 279. Original image from Supplementary Fig. S14. Artwork by Lewis Long.