Myelodysplastic syndrome (MDS) is a group of bone marrow disorders where the bone marrow is incapable of producing healthy mature blood cells. Through a process called hematopoiesis, blood stem cells or hematopoietic stem and progenitor cells (HSPC) within the bone marrow give rise to blood cells, such as white blood cells, platelets, and red blood cells. In an individual with MDS the HSPCs fail to mature and either die in the bone marrow or soon after they enter the bloodstream. The lack of blood cells leads to infection, anemia, excess bleeding, spontaneous bruising, and, in some cases, acute myeloid leukemia (AML).
No cure exists due to the complexity of the pathogenesis of MDS. Standard care comprises of blood transfusions along with treatment of the symptoms caused by the infection to improve the patients’ quality of life. More aggressive treatments exist and include stem cell transplants and aggressive chemotherapy. However, the aggressiveness of such treatments leads to a high mortality rate in the elderly and are generally reserved for younger high-risk patients.
Recent studies have shown a link between the accumulation of CD33+ myeloid-derived suppressor cells (MDSC) in the bone marrow microenvironment and MDS. Additionally, CD33+ MDSCs secrete immune-suppressive cytokines that contribute to mediated hematopoietic suppressive function in MDS. Consequently, the accumulation of CD33+ MDSCs and their suppressive function results in ineffective hematopoiesis in the bone marrow leading to the death of HSPCs.
In an article published in Leukemia, Eksioglu et al. report that blocking myeloid-derived suppressor cell (MDSC)-mediated hematopoietic suppressive function improves the bone marrow microenvironment in MDS samples. Using a human Fc-engineered monoclonal antibody against CD33 (BI 836585), which binds and blocks CD33 signaling, prevented immune-suppressive cytokine secretion in CD33+ MDSCs. The binding of BI 836585 reduced CD33+ MDSCs by triggering antibody-dependent cellular toxicity (ADCC). Furthermore, MDS bone marrow mononuclear cells cultured with BI 836585 revealed ex vivo hematopoiesis, which demonstrates the positive effects of this antibody on HSPC maturation. Conversely, when co-cultured with StemExpress’ bone marrow CD34+ hematopoietic stem cells, the presence of the antibody had a slight negative effect on the differentiation of myeloid cells, suggesting that some of the HSPC population may express CD33 and are targeted for ADCC.
The authors show that the use of clone BI 836585 blocks the functionality of CD33+ MDSCs, decreases the number of CD33+ MDSCs, and improves hematopoiesis of HSPCs ex vivo of MDS samples, which suggests that CD33 downstream signaling plays a role in the pathogenesis of MDS. This demonstrates that CD33 antibody-based therapy directed at MDSCs is a promising treatment for MDS and sets the foundation for further testing and clinical trials. Development of a new treatment for MDS patients has the potential to increase their quality of life without undergoing aggressive treatments that may have detrimental effects.
StemExpress is a life-science company dedicated to advancing medical science. We are proud to support medical research with our products, and excited that our Bone Marrow CD34+ Stem Cells were used in a project that aims to improve the quality of life of those inflicted with a debilitating disease.
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