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 language | English (US) |
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Pages (from-to) | 480-489 |
Number of pages | 10 |
Journal | Blood Reviews |
Volume | 32 |
Issue number | 6 |
DOIs | |
State | Published - Nov 2018 |
Keywords
- Apoptosis
- CD47
- Hematologic malignancy
- Immunotherapy
- Leukemic stem cell
- Monoclonal antibody
- Phagocytosis
ASJC Scopus subject areas
- Hematology
- Oncology