Preclinical efficacy of humanized, non–FcγR-binding anti-CD3 antibodies in T-cell acute lymphoblastic leukemia

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that accounts for about 20% ALL cases. Intensive chemotherapy regimens result in >85% cure rates in children and <50% in adults, calling for the search of novel therapeutic strategies. While immune-based therapies have tremendously improved the treatment of B-ALL and other B-cell malignancies, they are not available yet in T-ALL. We report here that humanized, non-FcgR binding monoclonal antibodies to CD3 have anti-leukemic properties in xenograft (PDX) models of CD3+ T-ALL, resulting in prolonged host survival. We also report that these antibodies cooperate with chemotherapy to enhance anti-leukemic effects and host survival. As these antibodies show only minor, manageable side effects in humans, they offer a new therapeutic option for the treatment of T-ALL. Our results also show that the anti-leukemic properties of anti-CD3 mAbs are largely independent Fcg-receptor mediated pathways in T-ALL PDX.