ArticleJournal of hematology & oncology2021
SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells.
Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- The Application of Nanomaterials in Breast Cancer.Pharmaceutics · 2025Review
- IGSF9-targeted therapy inhibits the progression of acute myeloid leukemia.Blood advances · 2025Article
- Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments.Signal transduction and targeted therapy · 2025Review
- Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.Cancer cell international · 2025Review
- Targeting myeloid cells for hematological malignancies: the present and future.Biomarker research · 2025Review
- Deciphering the secrets of tumor-initiating cells in pancreatic ductal adenocarcinoma microenvironment: mechanisms and therapeutic opportunities.Frontiers in immunology · 2025Review
- Bone marrow immune cells and drug resistance in acute myeloid leukemia.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives.Frontiers in oncology · 2024Review
- Updates in novel immunotherapeutic strategies for relapsed/refractory AML.Frontiers in oncology · 2024Review
- Comprehensive analysis of clinical prognostic features and tumor microenvironment landscape of CD11bCellular oncology (Dordrecht, Netherlands) · 2023Article
- Building on the backbone of CD47-based therapy in cancer: Combination strategies, mechanisms, and future perspectives.Acta pharmaceutica Sinica. B · 2023Review
- Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer.Frontiers in pharmacology · 2023Article
- A perspective of immunotherapy for acute myeloid leukemia: Current advances and challenges.Frontiers in pharmacology · 2023Review
- Crystal Structure of Human CD47 in Complex with Engineered SIRPα.D1(N80A).Molecules (Basel, Switzerland) · 2022Article
- Targeting macrophages in hematological malignancies: recent advances and future directions.Journal of hematology & oncology · 2022Review
- Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia.Experimental hematology & oncology · 2022Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAcute myeloid leukaemia (AML) stem cells (LSCs) cause disease relapse. The CD47 "don't eat me signal" is upregulated on LSCs and contributes to immune evasion by inhibiting phagocytosis through interacting with myeloid-specific signal regulatory protein alpha (SIRPα). Activation of macrophages by blocking CD47 has been successful, but the ubiquitous expression of CD47 on healthy cells poses potential limitations for such therapies. In contrast, CD123 is a well-known LSC-specific surface marker utilized as a therapeutic target. Here, we report the development of SIRPα-αCD123 fusion antibodies that localize the disruption of CD47/SIRPα signalling to AML while specifically enhancing LSC clearance.
methodsSIRPα-αCD123 antibodies were generated by fusing the extracellular domain of SIRPα to an αCD123 antibody. The binding properties of the antibodies were analysed by flow cytometry and surface plasmon resonance. The functional characteristics of the fusion antibodies were determined by antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity assays using primary AML patient cells. Finally, an in vivo engraftment assay was utilized to assess LSC targeting.
resultsSIRPα-αCD123 fusion antibodies exhibited increased binding and preferential targeting of CD123
conclusionsSIRPα-αCD123 antibodies combine local CD47 blockade with specific LSC targeting in a single molecule, minimize the risk of targeting healthy cells and efficiently eliminate AML LSCs. These results validate SIRPα-αCD123 antibodies as promising therapeutic interventions for AML.
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