Journal of Clinical and Cellular Immunology
Open Access

Novel therapeutic approach to improve hematopoiesis by targeting MDSCs with the novel Fcengineered CD33 antibody BI 836858 in MDS

9^th European Immunology Conference Associated with Antibody Engineering Meeting

June 14-16, 2018 | Rome, Italy

Sheng Wei, Erika A Eksioglu, Jinhong Liu, Karl-Heinz Heider, Bjoern Rueter, Jin Qi, Pinyang Cheng, Jeffrey Lancet, Rami Komrokji, Julie Djeu and Alan List

H. Lee Moffitt Cancer Center and Research Institute, USA
Boehringer Ingelheim, Germany

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

We recently reported that, the accumulation of myeloid-derived suppressor cells (MDSCs), defined as CD33+HLA-DRâ�?�? Linâ�?�?, play a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is greatly expressed in MDSC isolated from patients with MDS and plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by its ligand S100A9. Therefore, we tested the hypothesis that 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 found that BI 836858 can reduce MDSC by antibody-dependent cytotoxicity (ADCC), which correlated with an increase in granule mobilization and increased cytotoxicity. BI 836858 can also block CD33â�?�?s downstream signaling and prevent immune-suppressive cytokine secretion, which correlates with a significant increase in the formation of colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit erythroid (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 level of double strand breaks and adducts (measured by comet assay, �?³H2AX and 8-oxoguanidine). This work provides the ground for the development of a novel group of therapies aimed at MDSC and their signaling with the long term goal of improving hematopoiesis.