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Blocking 'don't eat me' signal of CD47-SIRPα in hematological malignancies, an in-depth review
- Source :
- Blood Reviews. 32:480-489
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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.
- Subjects :
- 0301 basic medicine
medicine.drug_class
medicine.medical_treatment
T cell
Antineoplastic Agents
Apoptosis
CD47 Antigen
Monoclonal antibody
Article
03 medical and health sciences
0302 clinical medicine
Immune system
Phagocytosis
Blocking antibody
Animals
Humans
Medicine
Molecular Targeted Therapy
Receptors, Immunologic
biology
business.industry
CD47
Hematology
Immunotherapy
Antigens, Differentiation
030104 developmental biology
medicine.anatomical_structure
Oncology
Hematologic Neoplasms
030220 oncology & carcinogenesis
biology.protein
Cancer research
Rituximab
Antibody
business
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 0268960X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Blood Reviews
- Accession number :
- edsair.doi.dedup.....ec9a9e2f4452a57b0e39587c943171c1