Targeting CD47 in Sézary syndrome with SIRPαFc

Blood Adv. 2019 Apr 9;3(7):1145-1153. doi: 10.1182/bloodadvances.2018030577.


Sézary 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 Sézary 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 Sézary cells is under the influence of interleukin 4 (IL-4), IL-7, and IL-13. Signal regulatory protein αFc (SIRPαFc; TTI-621), a novel CD47 decoy receptor, triggers macrophage-mediated phagocytosis of Sézary cells and, when administered in clinical trial settings, results in significant tumor load reduction. We conclude that inhibition of the CD47-SIRPα signaling pathway has therapeutic benefit for patients with SS. This trial was registered at as #NCT02663518.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD47 Antigen / antagonists & inhibitors
  • CD47 Antigen / drug effects
  • CD47 Antigen / metabolism
  • Cytokines / pharmacology
  • Female
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Macrophages / immunology
  • Male
  • Middle Aged
  • Phagocytosis
  • Sezary Syndrome / drug therapy*
  • Sezary Syndrome / mortality
  • Signal Transduction
  • Survival Analysis
  • Tumor Burden / drug effects


  • CD47 Antigen
  • CD47 protein, human
  • Cytokines
  • Immunoglobulin G
  • TTI-621

Associated data