Journal
BLOOD ADVANCES
Volume 3, Issue 7, Pages 1145-1153Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2018030577
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- Trillium Therapeutics Inc
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Sezary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma, has limited treatment options and rare occurrences of long-term remission, thus warranting research into new treatment approaches. CD47 has emerged as a promising target for multiple tumor types, but its role in SS remains unknown. Here, we show that CD47 is highly expressed on Sezary cells in the peripheral blood and skin, and the high level of CD47 expression correlates with worse overall survival (OS) in patients with SS. We also demonstrate that CD47 expression on Sezary cells is under the influence of interleukin 4 (IL-4), IL-7, and IL-13. Signal regulatory protein alpha Fc (SIRP alpha Fc; TTI-621), a novel CD47 decoy receptor, triggers macrophage-mediated phagocytosis of Sezary cells and, when administered in clinical trial settings, results in significant tumor load reduction. We conclude that inhibition of the CD47-SIRP alpha signaling pathway has therapeutic benefit for patients with SS.
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