Binding of an anti-CD3 antibody activates TCR signaling in medullary T-ALL leading to apoptosis of leukemic blasts through a program that resembles negative selection of thymocytes. Anti-CD3 antibodies teplizumab and foralumab produced robust antileukemic activity in PDX mouse models of sCD3⁺ T-ALL, suggesting a new therapeutic avenue for patients with this disease. mAb, monoclonal antibody.