Anti-BTN3A 20.1 Agonist Monoclonal Antibody Enhances Autologous Vγ9Vδ2 T Cells Cytotoxicity Against Primary Acute Myeloid Blasts

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.5153-5153
• Main Authors: Le Floch, Anne-Charlotte, Orlanducci, Florence, Briantais, Antoine, Le Roy, Aude, Chretien, Anne-Sophie, Vey, Norbert, Olive, Daniel
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-125541

Introduction: Vγ9Vδ2 T cells immunotherapy is an emerging strategy in acute myeloid leukemia (AML). Partial effects of phosphoantigens like zoledronate, prompted us to investigate other molecules. Using Vγ9Vδ2 T cells expanded from healthy volunteers, recent works of our team demonstrate that anti-BTN3A 20.1 agonist monoclonal antibody (mAb) improves Vγ9Vδ2 T cells cytotoxicity in vitro and in vivo, including in zoledronate resistant blasts. Efficacy of anti-BTN3A 20.1 agonist mAb remains undetermined using autologous Vγ9Vδ2 T cells and mechanism of its action on AML blasts is understudied. Material and methods: Expression of co-stimulatory molecules on surface of AML blasts and Vγ9Vδ2 T cells, from 37 PBMC of AML patients, was assessed by flow cytometry. Vγ9Vδ2 T cells expansion was realized from the same samples with zoledronate, and administrations of Il-2 and Il-15. Purity was assessed by flow cytometry at day 13. Degranulation assay was performed at day 14. Results: 20 degranulation assays were realized on successfully expanded Vγ9Vδ2 T cells (69% of analyzable samples). Degranulation with anti-BTN3A 20.1 agonist mAb was enhanced compared to zoledronate condition (p=0.0085) or negative control (p