CD47–SIRPα-targeted therapeutics: status and prospects

Maute, Roy L.; Xu, Jin; Weissman, Irving L.

doi:10.1016/j.iotech.2022.100070

Cited by 63 publications

(72 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, studies have shown that magrolimab can be safely administered at a low "priming" dose. A transient anemia accompanied by compensatory reticulocytosis was observed in these studies, but severe anemia was not observed at subsequent higher maintenance doses [96,97]. In addition, the updated ASCO abstract in 2022 also confirmed that HR-MDS patients treated with magrolimab in combination with AZA exhibit a tolerable anemia through priming and maintenance doses [98].…”

Section: Myelodysplastic Syndrome (Mds) and Acute Myeloid Leukemia (Aml)mentioning

confidence: 62%

Targeting macrophages in hematological malignancies: recent advances and future directions

Wang

Guo

et al. 2022

J Hematol Oncol

View full text Add to dashboard Cite

Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated immune escape. The most well-described innate immune checkpoints are the “don’t eat me” signals, including the CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 axis, and MHC-I/LILRB1 axis. Molecules have been developed to block these pathways and enhance the phagocytic activity against tumors. Several clinical studies have investigated the safety and efficacy of CD47 blockades, either alone or in combination with existing therapy in hematological malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and lymphoma. However, only a minority of patients have significant responses to these treatments alone. Combining CD47 blockades with other treatment modalities are in clinical studies, with early results suggesting a synergistic therapeutic effect. Targeting macrophages with bispecific antibodies are being explored in blood cancer therapy. Furthermore, reprogramming of pro-tumor macrophages to anti-tumor macrophages, and CAR macrophages (CAR-M) demonstrate anti-tumor activities. In this review, we elucidated distinct types of macrophage-targeted strategies in hematological malignancies, from preclinical experiments to clinical trials, and outlined potential therapeutic approaches being developed.

show abstract

Section: Myelodysplastic Syndrome (Mds) and Acute Myeloid Leukemia (Aml)mentioning

confidence: 62%

Targeting macrophages in hematological malignancies: recent advances and future directions

Wang

Guo

et al. 2022

J Hematol Oncol

View full text Add to dashboard Cite

show abstract

“…In addition to drug delivery system and bispecific antibody, there are many other strategies to prevent anemia caused by anti-CD47 therapeutics: gradually increase therapeutic dose ( 125 ); differentiate erythrocytes CD47 and tumor cell-expressing CD47 ( 114 , 126 – 130 ); sacrifice antibodies mediated ADCP (antibody-dependent cellular phagocytosis) ( 131 – 133 ); pro-body technology ( 134 ) ( 120 ). Apart from anemia, issues with thrombocytopenia, hyperbilirubinemia, and neutropenia have also limited the use of anti-CD47.…”

Section: Side Effects Of Anti-cd47 Treatments and Proposed Solutionsmentioning

confidence: 99%

CD47 as a promising therapeutic target in oncology

Zhao

Song

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

CD47 is ubiquitously expressed on the surface of cells and plays a critical role in self-recognition. By interacting with SIRPα, TSP-1 and integrins, CD47 modulates cellular phagocytosis by macrophages, determines life span of individual erythrocytes, regulates activation of immune cells, and manipulates synaptic pruning during neuronal development. As such, CD47 has recently be regarded as one of novel innate checkpoint receptor targets for cancer immunotherapy. In this review, we will discuss increasing awareness about the diverse functions of CD47 and its role in immune system homeostasis. Then, we will discuss its potential therapeutic roles against cancer and outlines, the possible future research directions of CD47- based therapeutics against cancer.

show abstract

“…In particular, magrolimab (Hu5F9-G4, ONO-7913) is a humanized monoclonal antibody that binds CD47 at low nanomolar affinity and is built on an IgG4 scaffold to minimize Fc-mediated effector toxicity for non-tumor cells expressing CD47 [ 117 ]. In immunodeficient mice models, magrolimab shows strong monotherapy activity against human hematological malignancies [ 118 ].…”

Section: The Cd47 Receptormentioning

confidence: 99%

Targeting CXCR4 and CD47 Receptors: An Overview of New and Old Molecules for a Biological Personalized Anticancer Therapy

Leo

Sabatino

2022

IJMS

View full text Add to dashboard Cite

Biological therapy, with its multifaceted applications, has revolutionized the treatment of tumors, mainly due to its ability to exclusively target cancer cells and reduce the adverse effects on normal tissues. This review focuses on the therapies targeting the CXCR4 and CD47 receptors. We surveyed the results of early clinical trials testing compounds classified as nonpeptides, small peptides, CXCR4 antagonists or specific antibodies whose activity reduces or completely blocks the intracellular signaling pathways and cell proliferation. We then examined antibodies and fusion proteins against CD47, the receptor that acts as a “do not eat me” signal to phagocytes escaping immune surveillance. Despite these molecules being tested in early clinical trials, some drawbacks are emerging that impair their use in practice. Finally, we examined the ImmunoGenic Surrender mechanism that involves crosstalk and co-internalization of CXCR4 and CD47 upon engagement of CXCR4 by ligands or other molecules. The favorable effect of such compounds is dual as CD47 surface reduction impact on the immune response adds to the block of CXCR4 proliferative potential. These results suggest that a combination of different therapeutic approaches has more beneficial effects on patients’ survival and may pave the way for new accomplishments in personalized anticancer therapy.

show abstract

CD47–SIRPα-targeted therapeutics: status and prospects

Cited by 63 publications

References 111 publications

Targeting macrophages in hematological malignancies: recent advances and future directions

Targeting macrophages in hematological malignancies: recent advances and future directions

CD47 as a promising therapeutic target in oncology

Targeting CXCR4 and CD47 Receptors: An Overview of New and Old Molecules for a Biological Personalized Anticancer Therapy

Contact Info

Product

Resources

About