title: BTN3A molecules considerably improve Vγ9Vδ2T cells-based immunotherapy in acute myeloid leukemia.
abstract: Given their recognized ability to kill acute myeloid leukemia (AML) blasts bothin vitroandin vivo, Vγ9Vδ2 T cells are of growing interest in the design of new strategies of immunotherapy. We show that the Butyrophilin3A (BTN3A, CD277) subfamily is a critical determinant of Vγ9Vδ2 TCR-mediated recognition of human primary AML blastsex vivo. Moreover, anti-BTN3A 20.1 agonist monoclonal antibodies (mAbs) can trigger BTN3A on AML blasts leading to further enhanced Vγ9Vδ2 T cell-mediated killing, but this mAb had no enhancing effect upon NK cell-mediated killing. We show that monocytic differentiation of primary AML blasts accounts for their AminoBisphosphonate (N-BP)-mediated sensitization to Vγ9Vδ2 T cells. In addition, anti-BTN3A 20.1 mAbs could specifically sensitize resistant blasts to Vγ9Vδ2 T cells lysis and overcome the poor effect of N-BP treatment on those blasts. We confirmed the enhancement of Vγ9Vδ2 T cells activity by anti-BTN3A 20.1 mAb using a human AML xenotransplantation mouse model. We showed that anti-BTN3A 20.1 mAb combined with Vγ9Vδ2 T cells immunotherapy could increase animal survival and decrease the leukemic burden in blood and bone marrow. These findings could be of great interest in the design of new immunotherapeutic strategies for treating AML.
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Benyamine
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Le Roy
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), molecular Oncology, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Gertner-Dardenne
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Castanier
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Orlanducci
authors.affiliation: Inserm, U1068, CRCM, TrGET Plateforme d'Essais Précliniques, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pouyet
authors.affiliation: Inserm, U1068, CRCM, TrGET Plateforme d'Essais Précliniques, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Goubard
authors.affiliation: Inserm, U1068, CRCM, TrGET Plateforme d'Essais Précliniques, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Collette
authors.affiliation: Aix-Marseille Univ, Marseilles, France; Institut Paoli Calmettes, Marseilles, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: Inserm, U892 , Nantes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scotet
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105 , CNRS UMR 7258 , Marseilles, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Castellano
authors.affiliation: Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes, Aix-Marseille Université UM 105, CNRS UMR 7258, Marseilles, France; Inserm, U1068, CRCM, TrGET Plateforme d'Essais Précliniques, Institut Paoli-Calmettes, Aix-Marseille Université UM 105, CNRS UMR 7258, Marseilles, France; Aix-Marseille Univ, Marseilles, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
keywords: Acute myeloid leukemia; BTN3A; aminobisphosphonate; immunotherapy; monoclonal antibody; γδT cells