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Targeting CD47 in Sézary syndrome with SIRPαFc

Lisa D S Johnson1, Swati Banerjee2, Oleg Kruglov2

  • 1Trillium Therapeutics Inc, Mississauga, ON, Canada.

Blood Advances
|April 10, 2019
PubMed

Insights

Sézary syndrome (SS) treatment is limited. Targeting CD47, highly expressed on SS cells, with SIRPαFc (TTI-621) shows promise by enabling phagocytosis and reducing tumor load.

Area of Science:

  • Oncology
  • Immunology
  • Dermatology

Background:

  • Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma, presents limited therapeutic options and infrequent long-term remission.
  • The CD47 protein is a potential therapeutic target in various cancers, but its significance in SS is not yet understood.

Purpose of the Study:

  • To investigate the expression and role of CD47 in Sézary syndrome.
  • To evaluate the therapeutic potential of targeting the CD47-SIRPα signaling pathway in SS.

Main Methods:

  • Analysis of CD47 expression on Sézary cells from peripheral blood and skin.
  • Assessment of the correlation between CD47 levels and overall survival (OS).
  • Investigation of cytokine (IL-4, IL-7, IL-13) influence on CD47 expression.
  • Evaluation of Signal regulatory protein αFc (SIRPαFc; TTI-621) in promoting macrophage-mediated phagocytosis and tumor reduction in a clinical trial setting (NCT02663518).

Main Results:

  • CD47 is highly expressed on Sézary cells, and elevated expression correlates with poorer OS in SS patients.
  • Interleukins IL-4, IL-7, and IL-13 were found to influence CD47 expression on Sézary cells.
  • SIRPαFc (TTI-621) effectively induced phagocytosis of Sézary cells by macrophages.
  • Clinical administration of SIRPαFc led to a significant reduction in tumor burden.

Conclusions:

  • Inhibition of the CD47-SIRPα pathway offers a promising therapeutic strategy for Sézary syndrome.
  • Targeting CD47 represents a viable approach to enhance anti-tumor immunity in SS.

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