| Literature DB >> 29709247 |
Atlantis Russ1, Anh B Hua2, William R Montfort3, Bushra Rahman4, Irbaz Bin Riaz5, Muhammad Umar Khalid6, Jennifer S Carew7, Steffan T Nawrocki8, Daniel Persky9, Faiz Anwer10.
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.Entities:
Keywords: Apoptosis; CD47; Hematologic malignancy; Immunotherapy; Leukemic stem cell; Monoclonal antibody; Phagocytosis
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Year: 2018 PMID： 29709247 PMCID： PMC6186508 DOI： 10.1016/j.blre.2018.04.005
Source DB: PubMed Journal: Blood Rev ISSN： 0268-960X Impact factor: 8.250