Targeting CD47 in Sézary syndrome with SIRPαFc Journal Article

   


Authors: 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.
Article Title: Targeting CD47 in Sézary syndrome with SIRPαFc
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. © 2019 by The American Society of Hematology.
Keywords: adult; cancer survival; clinical article; controlled study; human tissue; protein expression; aged; unclassified drug; human cell; overall survival; pathogenesis; antineoplastic agent; gene overexpression; interleukin 13; interleukin 4; interleukin 7; in vitro study; skin; blood; th2 cell; macrophage; phagocytosis; ex vivo study; regulator protein; cd47 antigen; sezary syndrome; human; male; female; priority journal; article; tti 621; signal regulatory protein alphafc; protein expression level; sezary cell
Journal Title: Blood Advances
Volume: 3
Issue: 7
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2019-04-09
Start Page: 1145
End Page: 1153
Language: English
DOI: 10.1182/bloodadvances.2018030577
PUBMED: 30962222
PROVIDER: scopus
PMCID: PMC6457236
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068306965&doi=10.1182%2fbloodadvances.2018030577&partnerID=40&md5=d9d88f4888319e2b95b874c2e100f3f5
Notes: Article -- Export Date: 2 August 2019 -- Source: Scopus
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MSK Authors
  1. Steven M Horwitz
    645 Horwitz
  2. Alexander Meyer Lesokhin
    363 Lesokhin
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