ArticleJournal for immunotherapy of cancer2022
Ligufalimab, a novel anti-CD47 antibody with no hemagglutination demonstrates both monotherapy and combo antitumor activity.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 39 citations in OpenAlex.
- PRDM1+ Malignant Cells Mediate an Immunosuppressive Landscape and Resistance to Neoadjuvant Chemoradiotherapy and Immunotherapy in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Trial
- CD47 is a regulator in doxorubicin-induced cardiac aging in male mice.Physiological reports · 2026Article
- Bispecific Antibodies for Acute Myeloid Leukemia: From Bone Marrow Immune Niche to Clinical Translation.Antibodies (Basel, Switzerland) · 2026Review
- Targeting the CD47-SIRPα phagocytic checkpoint in cancer: Biology, translational opportunities, and next-generation therapeutic strategies.Smart molecules : open access · 2026Review
- Tumor-associated protease-activated anti-CD47 antibody precisely maintains phagocytic ability of macrophages with minimal effect on healthy tissue.Journal of translational medicine · 2026Article
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies.Journal of hematology & oncology · 2026Article
- The SIRP family: from structural diversity and signaling mechanisms to implications in immune-related disease targeted therapeutics.Frontiers in immunology · 2026Review
- The CD47 signaling axis regulates the formation and vulnerability of atherosclerotic plaques: mechanism analysis and targeting strategies.Frontiers in immunology · 2026Review
- Therapeutic biologics interference in serological and pre-transfusion testing.Frontiers in immunology · 2026Review
- TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.Frontiers in oncology · 2026Review
- Intraperitoneal programming of tailored CAR macrophages via mRNA lipid nanoparticle to boost cancer immunotherapy.Nature communications · 2025Article
- Glutathione-Responsive Folate-Targeted Prodrugs: Tumor-Specific PD-L1 and CD47 Blockade.Molecules (Basel, Switzerland) · 2025Article
- Innovative organ-on-a-chip platforms for exploring tumorigenesis and therapy in head and neck cancer.Journal of translational medicine · 2025Review
- Targeting acute myeloid leukemia through antibody engineering: innovations in immunotherapy and combination regimens.Clinical and experimental medicine · 2025Review
- Development of a Novel Bifunctional Anti-CD47 Fusion Protein with Improved Efficacy and a Favorable Safety Profile.Molecular cancer therapeutics · 2025Article
- Targeting myeloid cells for hematological malignancies: the present and future.Biomarker research · 2025Review
- Preclinical Development of SGN-CD47M: Protease-Activated Antibody Technology Enables Selective Tumor Targeting of the Innate Immune Checkpoint Receptor CD47.Molecular cancer therapeutics · 2025Article
- Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment.Small science · 2025Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD47 is a widely expressed transmembrane glycoprotein that delivers an antiphagocytic signal on macrophages through its interaction with SIRPα. CD47 is highly expressed in cancer cells and its overexpression is correlated with poor prognosis. CD47 blocking antibodies are actively being developed worldwide for cancer therapy, and the most challenging concern is associated with hematotoxicity. Ligufalimab (AK117) is a novel humanized IgG4 anti-CD47 antibody without hemagglutination effect. Blockade of CD47-SIRPα pathway by AK117 leads to a promising therapeutic strategy for cancer treatment with unique safety features.
methodsAK117 was discovered through a screening hierarchy excluding hemagglutination. AK117 was characterized by detecting CD47-SIRPα blocking potential. Its effect on human red blood cells was examined and the mechanism of its binding with erythrocytes was studied. The abilities of AK117 and its combination with various opsonizing antibodies to promote macrophage-dependent phagocytosis of multiple human tumor cells were determined using fluorescence microscopy and flow cytometry. In vivo, the antitumor efficacy of AK117 monotherapy and combination with AK112 (an anti-PD-1/VEGF-A bispecific antibody) was assessed in a variety of xenograft models. Toxicologic studies were evaluated in non-human primates.
resultsAK117 bound to CD47 with high affinity and blocked the CD47-SIRPα interaction. AK117 did not induce hemagglutination and showed significantly lower degree of erythrophagocytosis compared with Hu5F9-G4, and this mechanism of hemagglutination resistance might be related to the binding conformation. AK117 enhanced macrophage-mediated phagocytosis in both hematologic cancer and solid tumor cell lines as a single agent or in combination with cetuximab and rituximab in vitro, respectively. The antitumor effects of AK117 as a single agent or in combination with AK112 were also encouraging in various xenograft models. In non-human primates, AK117 showed less hematotoxicity compared with Hu5F9-G4.
conclusionsAK117 eliminated hemagglutination and also enabled to maintain full effectiveness of CD47 blockade on tumor cells, which resulted in excellent antitumor efficacy and favorable safety profile of AK117. A series of clinical trials of AK117 as a therapeutic agent in combination with various agents such as AK112 are in progress for the treatment of multiple hematologic malignancies and solid tumors.
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