Relapsed/refractory T-cell malignancies have a particularly poor prognosis and novel therapies are direly needed. CD5 is a great candidate for adoptive cellular therapy to target T-cell malignancies since it is ubiquitously expressed on T cells with restricted expression on other hematopoietic cells. NK cells are an attractive platform for CAR engineering to target CD5 since, unlike T cells, they do not express CD5 on their surface, which eliminates the risk of fratricide. Another advantage of NK cells for CAR engineering is their safety profile; in contrast to T cells, they do not cause cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) and they are not associated with graft-versus-host disease (GVHD) in the allogeneic setting, opening the potential for a completely off-the-shelf cellular product to be used at point of care. Therefore, we sought to develop CD5 targeting CAR-NK cells for the treatment of T-cell malignancies.