Preclinical efficacy of humanized, non-FcγR-binding anti-CD3 antibodies in T-cell acute lymphoblastic leukemia
- 10 September 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 136 (11), 1298-1302
- https://doi.org/10.1182/blood.2019003801
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that accounts for similar to 20% of ALL cases. Intensive chemotherapy regimens result in cure rates >85% in children and <50% in adults, warranting a search of novel therapeutic strategies. Although immune-based therapies have tremendously improved the treatment of B-ALL and other B-cell malignancies, they are not yet available for T-ALL. We report here that humanized, non-Fc gamma receptor (Fc gamma R)-binding monoclonal antibodies (mAbs) to CD3 have antileukemic 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 antileukemic effects and host survival. Because these antibodies show only minor, manageable adverse effects in humans, they offer a new therapeutic option for the treatment of T-ALL. Our results also show that the antileukemic properties of anti-CD3 mAbs are largely independent of Fc gamma R mediated pathways in T-ALL PDXs.This publication has 24 references indexed in Scilit:
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