Blocking 'don't eat me' signal of CD47-SIRPα in hematological malignancies, an in-depth review
| Autor: | Atlantis Dawn Russ, Muhammad Umar Khalid, Faiz Anwer, Daniel O. Persky, Bushra Rahman, Irbaz Bin Riaz, William R. Montfort, Jennifer S. Carew, Anh Hua, Steffan T. Nawrocki |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Blood Reviews. 32:480-489 |
| ISSN: | 0268-960X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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