Immunotherapeutic co-targeting of CD38 and CD47 in T-cell acute lymphoblastic leukemia
(T-ALL)
Authors
K Müller
1
Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts University
Kiel and University Hospital Schleswig-Holstein, Campus Kiel
F Vogiatzi
1
Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts University
Kiel and University Hospital Schleswig-Holstein, Campus Kiel
D Winterberg
1
Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts University
Kiel and University Hospital Schleswig-Holstein, Campus Kiel
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
G Cario
1
Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts University
Kiel and University Hospital Schleswig-Holstein, Campus Kiel
M Schrappe
1
Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts University
Kiel and University Hospital Schleswig-Holstein, Campus Kiel
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
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
C Kellner
3
Department of Transfusion Medicine, Cell Therapeutics and Hemostaseology, University
Hospital, LMU Munich, Munich, Germany
DM Schewe
1
Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts University
Kiel and University Hospital Schleswig-Holstein, Campus Kiel
Aim Elevated surface expression of CD38 and the “don´t-eat-me” protein CD47 have been
described in T-ALL, making both targets attractive candidates for antibody therapy.
Methods: The CD38 antibody daratumumab (Dara) and a CD47 antibody (IgG2σ modified
Hu5F9-G4-clone) were examined for antibody-dependent effector mechanisms in T-ALL
cell lines and patient-derived xenograft (PDX) samples. Furthermore, NSG mice injected
with heterogenous T-ALL PDX cells were treated with Dara and a CD47 antibody with
and without chemotherapy. Results: Dara caused enhanced phagocytosis in antibody dependent
cellular phagocytosis (ADCP) assays. Using eight different PDX samples in a preclinical
phase II-like setting, Dara-monotherapy resulted in minimal residual disease negativity
in 50 % of the cases and substantial survival prolongation in xenograft mice. To further
improve ADCP, Dara was combined with a CD47 antibody. Thereby, phagocytosis in T-ALL
cell lines and in PDX cells was enhanced, which is subject of current in vivo investigations.
Conclusion: Dara represents a promising novel approach in antibody-based immunotherapy
for T-ALL patients, especially when combined with CD47 blockade.
