Klin Padiatr 2020; 232(03): e3
DOI: 10.1055/s-0040-1709769
Abstracts

Immunotherapeutic co-targeting of CD38 and CD47 in T-cell acute lymphoblastic leukemia (T-ALL)

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
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    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.


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    Publication History

    Article published online:
    13 May 2020

    © Georg Thieme Verlag KG
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