The existing CAR-engineered T cell-based (CAR-T) therapy represents one of the most successful immunotherapy approaches developed in recent years. Most CAR-T cell therapy has been used clinically to treat hematological malignancies by targeting the B cell-specific antigen, CD19. However, this approach is not without limitations due to toxicities such as by neurotoxicity or cytokine release syndrome. Additionally, CAR-T cells function only as autologous cells due to graft-versus-host disease that would develop if cells were obtained from another person. Therefore, CAR-T cells must be produced on a patient-specific basis. NK cells, on the other hand, function as allogenic cytotoxic effector cells that do not have to be utilized on a patient-specific basis and are proven to be less toxic since they do not cause cytokine release syndrome, neurotoxicity, or graft-versus-host disease. For these reasons, CAR-engineered NK (CAR-NK) cells have increasingly attracted interest as an alternative CAR-cell therapy. However, there exist other unmet challenges. Targeting CAR-based therapies against solid tumors has been challenging due to the lack of truly tumor-specific antigens as most targets are shared by non-malignant cells and can cause toxicity due to “on-target, off-tumor” effects.” A fine-tunable CAR therapy is useful to better identify and target tumors while limiting this toxicity.