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Antonia Rotolo, MD, PhD, University of Pennsylvania Veterinary School of Medicine, Philadelphia, PA, comments on the next steps in invariant natural killer T-cells (iNKTs) research. Dr Rotolo explains that currently, studies that have tested iNKTs in humans have reported very short persistence and it is therefore important to determine the best strategy to administer iNKTs, perhaps without eliminating endogenous immune cells with chemotherapy prior to iNKT infusion. It is also important to understand the impact of the effect mediated by iNKTs and by the host immune system. In addition, defining biomarkers to screen for optimal donors and achieve reproducible results with iNKT immunotherapy is also important. Finally, Dr Rotolo highlights the benefits of using canine models to accelerate the development of immunotherapies. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.