Journal
BLOOD REVIEWS
Volume 32, Issue 6, Pages 480-489Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2018.04.005
Keywords
CD47; Immunotherapy; Apoptosis; Phagocytosis; Leukemic stem cell; Monoclonal antibody; Hematologic malignancy
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Funding
- NCI NIH HHS [P30 CA023074] Funding Source: Medline
- NIGMS NIH HHS [R01 GM117357] Funding Source: Medline
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Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRP alpha triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody mediated blockade of CD47-SIRP alpha 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-SIRP alpha 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 (CD2O-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-SIRP alpha interaction in leukemia, lymphoma and multiple myeloma.
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