Targeting CD47 in Sézary syndrome with SIRPaFc

Lisa D.S. Johnson, Swati Banerjee, Oleg Kruglov, Natasja Nielsen Viller, Steven M. Horwitz, Alexander Lesokhin, Jasmine Zain, Christiane Querfeld, Robert Chen, Craig Okada, Ahmed Sawas, Owen A. O’Connor, Eric L. Sievers, Yaping Shou, Robert A. Uger, Mark Wong, Oleg E. Akilov

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 aFc (SIRPaFc; 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-SIRPa signaling pathway has therapeutic benefit for patients with SS. This trial was registered at www.clinicaltrials.gov as #NCT02663518.

Original languageEnglish (US)
Pages (from-to)1145-1153
Number of pages9
JournalBlood Advances
Volume3
Issue number7
DOIs
StatePublished - Apr 9 2019

ASJC Scopus subject areas

  • Hematology

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    Johnson, L. D. S., Banerjee, S., Kruglov, O., Viller, N. N., Horwitz, S. M., Lesokhin, A., Zain, J., Querfeld, C., Chen, R., Okada, C., Sawas, A., O’Connor, O. A., Sievers, E. L., Shou, Y., Uger, R. A., Wong, M., & Akilov, O. E. (2019). Targeting CD47 in Sézary syndrome with SIRPaFc. Blood Advances, 3(7), 1145-1153. https://doi.org/10.1182/bloodadvances.2018030577