Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies
In recent years, immunotherapies have been clinically investigated in AML and other myeloid malignancies. While most of these are focused on stimulating the adaptive immune system (including T cell checkpoint inhibitors), several key approaches targeting the innate immune system have been identified...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01380/full |
| _version_ | 1828842595670818816 |
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| author | Mark P. Chao Chris H. Takimoto Dong Dong Feng Kelly McKenna Phung Gip Jie Liu Jens-Peter Volkmer Irving L. Weissman Ravindra Majeti Ravindra Majeti |
| author_facet | Mark P. Chao Chris H. Takimoto Dong Dong Feng Kelly McKenna Phung Gip Jie Liu Jens-Peter Volkmer Irving L. Weissman Ravindra Majeti Ravindra Majeti |
| author_sort | Mark P. Chao |
| collection | DOAJ |
| description | In recent years, immunotherapies have been clinically investigated in AML and other myeloid malignancies. While most of these are focused on stimulating the adaptive immune system (including T cell checkpoint inhibitors), several key approaches targeting the innate immune system have been identified. Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. CD47 is a “do not eat me” signal, overexpressed in myeloid malignancies that leads to tumor evasion of phagocytosis by macrophages. Blockade of CD47 leads to engulfment of leukemic cells and therapeutic elimination. Pre-clinical data has demonstrated robust anti-cancer activity in multiple hematologic malignancies including AML and myelodysplastic syndrome (MDS). In addition, clinical studies have been underway with CD47 targeting agents in both AML and MDS as monotherapy and in combination. This review will describe the role of CD47 in myeloid malignancies and pre-clinical data supporting CD47 targeting. In addition, initial clinical data of CD47 targeting in AML/MDS will be reviewed, and including the first-in-class anti-CD47 antibody magrolimab. |
| first_indexed | 2024-12-12T20:26:35Z |
| format | Article |
| id | doaj.art-8638e8ad243d4633b048ad522ad22867 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T20:26:35Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8638e8ad243d4633b048ad522ad228672022-12-22T00:13:07ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-01-01910.3389/fonc.2019.01380494352Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid MalignanciesMark P. Chao0Chris H. Takimoto1Dong Dong Feng2Kelly McKenna3Phung Gip4Jie Liu5Jens-Peter Volkmer6Irving L. Weissman7Ravindra Majeti8Ravindra Majeti9Forty Seven, Inc., Menlo Park, CA, United StatesForty Seven, Inc., Menlo Park, CA, United StatesForty Seven, Inc., Menlo Park, CA, United StatesForty Seven, Inc., Menlo Park, CA, United StatesForty Seven, Inc., Menlo Park, CA, United StatesForty Seven, Inc., Menlo Park, CA, United StatesForty Seven, Inc., Menlo Park, CA, United StatesInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA, United StatesInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA, United StatesDivision of Hematology, Department of Medicine, Stanford, CA, United StatesIn recent years, immunotherapies have been clinically investigated in AML and other myeloid malignancies. While most of these are focused on stimulating the adaptive immune system (including T cell checkpoint inhibitors), several key approaches targeting the innate immune system have been identified. Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. CD47 is a “do not eat me” signal, overexpressed in myeloid malignancies that leads to tumor evasion of phagocytosis by macrophages. Blockade of CD47 leads to engulfment of leukemic cells and therapeutic elimination. Pre-clinical data has demonstrated robust anti-cancer activity in multiple hematologic malignancies including AML and myelodysplastic syndrome (MDS). In addition, clinical studies have been underway with CD47 targeting agents in both AML and MDS as monotherapy and in combination. This review will describe the role of CD47 in myeloid malignancies and pre-clinical data supporting CD47 targeting. In addition, initial clinical data of CD47 targeting in AML/MDS will be reviewed, and including the first-in-class anti-CD47 antibody magrolimab.https://www.frontiersin.org/article/10.3389/fonc.2019.01380/fullCD47AMLMDSmacrophageimmunotherapyleukemia stem cell (LSC) |
| spellingShingle | Mark P. Chao Chris H. Takimoto Dong Dong Feng Kelly McKenna Phung Gip Jie Liu Jens-Peter Volkmer Irving L. Weissman Ravindra Majeti Ravindra Majeti Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies Frontiers in Oncology CD47 AML MDS macrophage immunotherapy leukemia stem cell (LSC) |
| title | Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies |
| title_full | Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies |
| title_fullStr | Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies |
| title_full_unstemmed | Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies |
| title_short | Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies |
| title_sort | therapeutic targeting of the macrophage immune checkpoint cd47 in myeloid malignancies |
| topic | CD47 AML MDS macrophage immunotherapy leukemia stem cell (LSC) |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01380/full |
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