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Novel Therapeutic Approaches Targeting MDSC in Myelodysplastic Syndrome

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Technical Report,01 Sep 2015,31 Aug 2019

Corporate Author:

H. Lee Moffitt Cancer Center and Research Institute Tampa United States

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Development of targeted MDS therapies has been challenged by a limited insight of molecular mechanisms of disease pathogenesis and therefore, current therapeutic approaches remain highly empiric largely ignoring the role of the inflammatory bone marrowBM microenvironment. We identified S100A9 as a mediator of myeloid derived suppressor cell MDSC activation and as the native ligand to CD33, which is highly expressed in MDS. Therefore, our goals are to develop novel therapeutic strategies that inactivate MDSC to improve survival of HSPC and allow us to provide the basis for more effective, biologically rational MDS therapeutics. Based on our initial hypothesis of hematopoietic improvement through the targeting of the S100A9-CD33 pathway, this funding year we were able show that our proposed approaches can inactivate MDSC in vitro. This is achieved through the development of a specific S100A9 trap, the CD33-chimeric human IgG1 molecule CD33-fusion.

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  • Medicine and Medical Research

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