With the approval of CD19-targeted chimeric antigen receptor (CAR) T cells for the treatment of B cell malignancies, clinicians have gained valuable insights into the power and challenges of cellular therapies. In this issue of the JCI, Maluski et al. showed that a CAR containing a CD28 costimulatory domain drives progeny differentiation to resemble that of NK cells, which have the potential for an off-the-shelf cell therapy. These CAR-induced killer (CARiK) cells displayed potent antitumor function and killed across the MHC barrier in vivo. After performing in vitro and in vivo mouse studies, the authors also successfully differentiated human umbilical cord blood–derived progenitor cells into CARiK cells. These unique cells may address some of the current challenges associated with first-generation CARs, such as prolonged production that requires patients to wait weeks for infusion. We believe this innovative progenitor gene-engineered lymphoid system has the potential for clinical translation.