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 ∼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-Fcγ receptor (FcγR)-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 FcγR-mediated pathways in T-ALL PDXs.

• Authors: Christine Tran Quang, Benedetta Zaniboni, Romain Humeau, Etienne Lengliné, Marie Emilie Dourthe, Rajkumar Ganesan, Sanjaya Singh, Justin M Scheer, Vahid Asnafi, Jacques Ghysdael
• Journal: Blood (Blood) Vol. 136 Issue 11 Pg. 1298-1302 (09 10 2020) ISSN: 1528-0020 [Electronic] United States
• PMID: 32483610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• CD3 Complex
• Vincristine
• Dexamethasone
• foralumab
• teplizumab

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Antibodies, Monoclonal, Humanized (immunology, therapeutic use)
• Antineoplastic Agents, Immunological (immunology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• CD3 Complex (antagonists & inhibitors, immunology)
• Combined Modality Therapy
• Dexamethasone (administration & dosage)
• Dose-Response Relationship, Immunologic
• Female
• Humans
• Mice
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, immunology)
• Specific Pathogen-Free Organisms
• Vincristine (administration & dosage)
• Xenograft Model Antitumor Assays