Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. Development of CAR-T cell platforms to treat T-cell malignancies often requires additional gene modification to overcome fratricide due to shared T-cell antigens on normal and malignant T-cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels on transduced T-cells while retaining strong cytotoxicity against CD5 …