Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies

J Heymann; F Vogiatzi; T Rösner; L Lenk; G Cario; M Schrappe; T Valerius; M Peipp; C Kellner; DM Schewe

doi:10.1055/s-0039-1687156

Klinische Pädiatrie, Table of Contents

Klin Padiatr 2019; 231(03): 164-165
DOI: 10.1055/s-0039-1687156

Abstracts

Georg Thieme Verlag KG Stuttgart · New York

Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies

J Heymann

¹Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

F Vogiatzi

¹Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

T Rösner

²Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

L Lenk

¹Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

G Cario

¹Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

M Schrappe

¹Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

T Valerius

²Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

M Peipp

²Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

C Kellner

²Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

,

DM Schewe

¹Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany

› Author Affiliations

Abstract

Full Text

Aim:

In B-cell-neoplasias, patients with high Bcl-2 expression often have a poor prognosis. This includes patients with double-hit lymphomas (DHL), Burkitt's lymphoma (BL) and t[17;19]-positive ALL. We examined the role of the Bcl-2 inhibitor Venetoclax (VTX) on the efficacy of therapeutic antibodies.

Methods:

Antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated phagocytosis (ADCP) were measured in cell line and PDX models of DHL, BL and t[17;19]-ALL with the antibodies Rituximab (RTX), Daratumumab (Dara) and CD19-DE (a proprietary engineered antibody) in combination with VTX. Effects of VTX on the ADCP capacities of Rituximab (RTX) and CD19-DE were examined in vivo in xenograft mice.

Results:

ADCC and CDC were not enhanced by VTX. Increased ADCP by human and murine macrophages were detected in DHL cell lines with VTX/RTX and VTX/Dara, in BL-PDX with VTX/RTX and in t[17;19]-PDX with VTX/CD19-DE. Mice treated with VTX/RTX and VTX/CD19-DE showed superior survival as compared to VTX, RTX or CD19-DE alone.

Conclusion:

VTX enhances the efficacy of antibodies in B-cell-malignancies in vitro and in vivo.