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Accession Number:

AD1064812

Title:

Novel Therapeutic Approaches Targeting MDSC in Myelodysplastic Syndrome

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Report Date:

2018-09-01

Abstract:

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 marrow(BM) 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). We demonstrated thatCD33-fusion is able to neutralize soluble S100A9 and suppresses S100A9 induced pro-inflammatory cytokine production as well as improve hematopoiesis.

Pages:

13

File Size:

1.57MB

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Distribution Statement:

Approved For Public Release

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