Cited by 66Acute Myeloid Leukemia ResearchImmune cells in cancerMultiple Myeloma Research and Treatments

Novel therapeutic approach to improve hematopoiesis in low risk MDS by targeting MDSCs with the Fc-engineered CD33 antibody BI 836858

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Eksioglu, E A, Chen, X, Heider, K-H, Rueter, B, McGraw, K L, Basiorka, A A, Wei, M, Burnette, A +6 more·2017·Leukemia

Abstract

We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33+HLA-DR-Lin-, has a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it has an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS. We observed that BI 836858 can reduce MDSC by antibody-dependent cellular cytotoxicity, which correlated with increases in granule mobilization and cell death. BI 836858 can also block CD33 downstream signaling preventing immune-suppressive cytokine secretion, which correlates with a significant increase in the formation of CFU-GM and BFU-E colonies. Activation of the CD33 pathway can cause reactive oxygen species (ROS)-induced genomic instability but BI 836858 reduced both ROS and the levels of double strand breaks and adducts (measured by comet assay and γH2AX). This work provides the ground for the development of a novel group of therapies for MDS aimed at MDSC and their disease-promoting properties with the goal of improving hematopoiesis in patients.

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Crossref · 10.1038/leu.2017.21

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  • MDSCs are sufficient to create an MDS phenotype in murine experiments, and targeting them or their expansion leads to reconstitution of normal hematopoiesis.

    “MDSCs are sufficient to create an MDS phenotype in murine experiments, and targeting them or their expansion leads to reconstitution of normal hematopoiesis.76,77”

    From Inflammatory bone marrow microenvironment (2019) · cites this paper as [77]

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Research works printed but not linked: 1

  1. [11]Chen X Eksioglu EA Zhou J Zhang L Djeu J Fortenbery N Induction of myelodysplasia by myeloid-derived suppressor cells The Journal of clinical investigation 2013 11 123 11 4595 4611 24216507 PMC3809779

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Authors
Eksioglu, E. A., Chen, X., Heider, K.-H., Rueter, B., McGraw, K. L., Basiorka, A. A., Wei, M., Burnette, A., Cheng, P., Lancet, J., Komrokji, R., Djeu, J., List, A., & Wei, S.
Affiliations
  • Moffitt Cancer Center (US)
  • Boehringer Ingelheim (Austria) (AT)
  • Boehringer Ingelheim (Germany) (DE)
  • University of South Florida (US)
Corresponding author
Wei, S
Venue
Leukemia
Published
2017-01-18
Volume
31
Issue
10
Pages
2172-2180
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
OpenAlex
W2577785715
Cited by
66
References
40
Citations by year
2026: 3 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 4
FWCI
6.72
Type
journal article
Language
en
Open access
Locations
  • Leukemia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (K01CA187020, P30CA076292)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
Keywords
myelodysplastic syndrome, myeloid-derived suppressor cells, CD33, S100A9, hematopoiesis, bone marrow microenvironment, antibody-dependent cellular cytotoxicity, genomic instability, reactive oxygen species, DNA double-strand breaks, immunosuppression, low-risk MDS
MeSH terms
Myeloid-Derived Suppressor Cells, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Bone Marrow, Female, Genetic Engineering, Hematopoiesis, Humans, Immunoglobulin Fc Fragments, Male, Middle Aged, Myelodysplastic Syndromes, Signal Transduction, Reactive Oxygen Species, Genomic Instability, Stem Cell Niche, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized, Sialic Acid Binding Ig-like Lectin 3

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