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
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
F Vogiatzi
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
T Rösner
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
L Lenk
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
G Cario
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
M Schrappe
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
T Valerius
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
M Peipp
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
C Kellner
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
DM Schewe
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
20 May 2019 (online)

Also available at
 

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.