The landscape overview of CD47-based immunotherapy for hematological malignancies

Abstract

Extensive clinical and experimental evidence suggests that macrophages play a crucial role in cancer immunotherapy. Cluster of differentiation (CD) 47, which is found on both healthy and malignant cells, regulates macrophage-mediated phagocytosis by sending a "don't eat me" signal to the signal regulatory protein alpha (SIRPα) receptor. Increasing evidence demonstrates that blocking CD47 interaction with SIRPα can enhance cancer cell clearance by macrophages. Additionally, inhibition of CD47/SIRPα interaction can increase antigen cross-presentation, leading to T-cell priming and an activated adaptive antitumor immune response. Therefore, inhibiting CD47/SIRPα axis has a significant impact on tumor immunotherapy. Studies on CD47 monoclonal antibodies are at the forefront of research, and impressive results have been obtained. Nevertheless, hematotoxicity, especially anemia, has become the most common adverse effect of the CD47 monoclonal antibody. More specific targeted drugs (i.e., bispecific antibodies, SIRPα/Fc fusion protein antibodies, and small-molecule inhibitors) have been developed to reduce hematotoxicity. Here, we review the present usage of CD47 antagonists for the treatment of lymphomas and hematologic neoplasms from the perspectives of structure, function, and clinical trials, including a comprehensive overview of the drugs in development.

CytoSignal Detects Locations and Dynamics of Ligand-Receptor Signaling at Cellular Resolution from Spatial Transcriptomic Data

“…Additionally, Gal-9 is directly related to the accumulation of macrophages in the liver and reduces hepatocellular damage [85,86]. Cd47 is a transmembrane receptor located on the cell surface that regulates phagocytosis through macrophages in the liver [87,88]. Importantly, VeloCytoSignal is able to leverage the velocity differences between ligand and receptor genes when calculating the velocity of the signaling interaction.…”

Inhibiting the GPI Transamidase Subunit GPAA1 Abolishes CD24 Surface Localization and Enhances Macrophage-Mediated Phagocytosis of Ovarian Cancer Cells

“…In contrast, CD47, another anti-phagocytic signal, is widely expressed across all cell types 10 . Thus, targeting CD24 may offer the advantage of fewer off-target effects, potentially reducing the risk of toxicity 64 .…”

miR‐101‐5p modulation of CD47 in diffuse large B‐cell lymphoma: Implications for anti‐CD47 immunotherapy and prognostication

“…1 Central to this emerging field is CD47's pivotal role as an anti-phagocytic signal, leading to the development of agents designed to disrupt the CD47-signal regulatory protein α (SIRPa) axis. [2][3][4][5][6] While these agents hold tremendous promise, the precise regulation of CD47 remains a subject of ongoing investigation, 7 potentially impacting the efficacy of CD47 therapeutics.…”

“…11 Unsatisfactory outcomes, particularly in specific DLBCL subtypes, coupled with limited success in salvage therapies, have prompted the emergence of immune checkpoint-targeted therapies. One promising avenue in this domain is the CD47/SIRPα pathway, [2][3][4][5][6] the innate immune checkpoint that has attracted considerable attention. Here, we present evidence that a microRNA (miRNA) miR-101-5p plays a role in regulating CD47 expression and immune cell response in DLBCL.…”