Abstract
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.
Highlights
Inhibition of phagocytosis occurs by CD47 binding to its cognate receptor Signal Regulatory Protein Alpha (SIRPα) on macrophages leading to tyrosine phosphatase activation and inhibition of myosin accumulation at the phagocytic synapse site, thereby preventing phagocytosis [1]
CD47 is a novel macrophage immune checkpoint that plays a broad role in cancer immune evasion across multiple cancer types and in myeloid malignancies
CD47 has been identified as an leukemia stem cell (LSC) marker in acute myeloid leukemia (AML)
Summary
Pre-clinical data has demonstrated robust anti-cancer activity in multiple hematologic malignancies including AML and myelodysplastic syndrome (MDS). Clinical studies have been underway with CD47 targeting agents in both AML and MDS as monotherapy and in combination. Initial clinical data of CD47 targeting in AML/MDS will be reviewed, and including the first-in-class anti-CD47 antibody magrolimab.
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