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ASH 2019 | Targeted desialylation as a therapeutic strategy in MM

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Michael O’Dwyer

Hypersialylation of multiple myeloma (MM) cells facilitates immune evasion. Michael O’Dwyer, MD, PhD, National University of Ireland, Galway, Ireland, explains how certain sialylated glycans can act as ligands for the sialic acid-binding immunoglobulin-like lectin (Siglec) receptors expressed by NK-cells (Siglec-7 and Siglec-9). From this knowledge, it was hypothesized that desialylation of MM cells or targeted interruption of Siglec expression could lead to enhanced NK-cell mediated cytotoxicity of MM cells. Data suggest that targeted desialylation is a novel therapeutic strategy worth exploring in MM. In particular, concurrent upregulation of CD38 provides a strong rationale for strategies employing targeted desialylation with CD38 monoclonal antibodies, such as daratumumab, with the goal of maximizing antibody-dependent cellular cytotoxicity. This interview took place at the American Society of Hematology (ASH) 2019 Annual Meeting and Exposition in Orlando, FL.

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