In this project, we have completed the early preclinical development of a novel “off-the-shelf” universal hematopoietic stem cell (HSC)-engineered invariant natural killer T (^UHSC-iNKT) cell therapy. Specifically, we have demonstrated the feasibility, safety, and cancer therapy potential of the proposed ^UHSC-iNKT cell therapy, and laid a foundation for its next-stage translational and clinical development. If successful, this new therapy has the potential to become a next-generation cancer immunotherapy for treating a broad range of cancers and a large population of patients.