Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review

Atlantis Russ, Anh B. Hua, William R. Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S. Carew, Steffan T. Nawrocki, Daniel Persky, Faiz Anwer

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.

Original languageEnglish (US)
Pages (from-to)480-489
Number of pages10
JournalBlood Reviews
Volume32
Issue number6
DOIs
StatePublished - Nov 2018

Keywords

  • Apoptosis
  • CD47
  • Hematologic malignancy
  • Immunotherapy
  • Leukemic stem cell
  • Monoclonal antibody
  • Phagocytosis

ASJC Scopus subject areas

  • Hematology
  • Oncology

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