ArticleJCI insight2020
Targeting macrophage checkpoint inhibitor SIRPα for anticancer therapy.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Immune checkpoint molecules signal regulatory protein alpha in the development of hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Cell components of tumor microenvironment in lung adenocarcinoma: Promising targets for small-molecule compounds.Chinese medical journal · 2025Review
- The Physiological and Therapeutic Role of CD47 in Macrophage Function and Cancer.Immunological investigations · 2025Review
- Liposome-mediated macrophage reprogramming: emerging strategies for chronic disease therapy.Frontiers in immunology · 2025Review
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- Pan-cancer analysis of phagocytosis regulators in female-specific cancers: a focus on HMGB2.Frontiers in immunology · 2025Article
- Therapeutic strategies targeting CD47-SIRPα signaling pathway in gastrointestinal cancers treatment.Journal of pharmaceutical analysis · 2025Review
- A human antibody specific for SIRPα reprograms macrophages and promotes antibody mediated anti-cancer activity.PloS one · 2025Article
- Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody.Scientific reports · 2024Article
- Bioconjugated Antibody-Trojan Immune Converter Enhance Cancer Immunotherapy with Minimized Toxicity by Programmed Two-Step Immunomodulation of Myeloid Cells.Advanced healthcare materials · 2024Article
- Targeting CD47 and Angiogenesis Demonstrates Effective Anti-Tumor Effect in Bladder Cancer.Biomedicines · 2024Article
- A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response.Antibody therapeutics · 2024Article
- Pathways for macrophage uptake of cell-free circular RNAs.Molecular cell · 2024Article
- Biomimetic Nano-Degrader Based CD47-SIRPα Immune Checkpoint Inhibition Promotes Macrophage Efferocytosis for Cardiac Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeting tumor‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review).International journal of oncology · 2024Review
- Nanomaterial-Driven Precision Immunomodulation: A New Paradigm in Therapeutic Interventions.Cancers · 2024Review
- Small molecule innate immune modulators in cancer therapy.Frontiers in immunology · 2024Review
- Blockade of SIRPα-CD47 axis by anti-SIRPα antibody enhances anti-tumor activity of DXd antibody-drug conjugates.PloS one · 2024Article
- The role of CD47 in non-neoplastic diseases.Heliyon · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CD47/signal regulatory protein α (Cd47/SIRPα)interaction provides a macrophage immune checkpoint pathway that plays a critical role in cancer immune evasion across multiple cancers. Here, we report the engineering of a humanized anti-SIRPα monoclonal antibody (1H9) for antibody target cancer therapy. 1H9 has broad activity across a wide range of SIRPα variants. Binding of 1H9 to SIRPα blocks its interaction with CD47, thereby promoting macrophage-mediated phagocytosis of cancer cells. Preclinical studies in vitro and in vivo demonstrate that 1H9 synergizes with other therapeutic antibodies to promote phagocytosis of tumor cells and inhibit tumor growth in both syngeneic and xenograft tumor models, leading to survival benefit. Thus, 1H9 can potentially act as a universal agent to enhance therapeutic efficacy when used in combination with most tumor-targeting antibodies. We report a comparison of anti-SIRPα and anti-CD47 antibodies in CD47/SIRPα double-humanized mice and found that 1H9 exhibits a substantially reduced antigen sink effect due to the limited tissue distribution of SIRPα expression. Toxicokinetic studies in nonhuman primates show that 1H9 is well tolerated, with no treatment-related adverse effects noted. These data highlight the clinical potential of 1H9 as a pan-therapeutic with the desired properties when used in combination with tumor-targeting antibodies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.