ArticleJournal of hematology & oncology2023
A pH-dependent anti-CD47 antibody that selectively targets solid tumors and improves therapeutic efficacy and safety.
Article in Journal of hematology & oncology, 2023. 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.
- An IgG-like fusion protein comprising an anti-spike S2 antibody and ACE2 exhibits potent and broad neutralization against SARS-CoV-2 and variants of concern.Antibody therapeutics · 2026Article
- Injectable Hydrogels for Breast Cancer Therapy: From Tumor Microenvironment-Responsive and Actively Targeted Drug Delivery to Immunotherapy and Theranostics.Pharmaceutics · 2026Review
- An oncolytic vaccinia virus encoding CD47 nanobody potentiates antitumor immunity in multiple myeloma.iScience · 2026Article
- Ir(III) Complexes Convert Cold to Hot Tumors via Ferroptosis/Necroptosis-Driven Immunogenic Cell Death and Photosensitized CD47 Downregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- Article
- Harnessing the innate immune system: a novel bispecific antibody targeting CD47 and CD24 for selective tumor clearance.Journal for immunotherapy of cancer · 2025Article
- Engineering TME-activated CD47-specific CAR macrophage via Arg1 promoter for safe and effective solid tumor immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Harnessing chimeric antigen receptor macrophages against solid tumors.Cancer communications (London, England) · 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
- The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response.Cancer biology & therapy · 2024Review
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8Journal for immunotherapy of cancer · 2024Article
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- The biological roles of CD47 in ovarian cancer progression.Cancer immunology, immunotherapy : CII · 2024Review
- Understanding the Specific Implications of Amino Acids in the Antibody Development.The protein journal · 2024Review
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Difference between Keratinized- and Non-Keratinized-Originating Epithelium in the Process of Immune Escape of Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2024Article
- Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe antiphagocytic molecule CD47 is overexpressed in a wide variety of cancer cells, and antibodies targeting CD47 for cancer therapies are currently under intensive investigation. However, owing to the ubiquitous expression of CD47 on healthy cells, anti-CD47 therapies often achieve only weak therapeutic benefits and can induce severe side effects. Here, we report the generation of a pH-dependent anti-CD47 antibody (BC31M4) which selectively binds to tumors under the acidic solid tumor microenvironment.
methodsBC31M4 was generated using antibody phage display and a pH-dependent selection strategy. The pH-dependent binding and blocking activities of BC31M4 were verified using in vitro assays, and the structural basis of the pH-dependent binding property was characterized. BC31M4's antitumor effect was confirmed by both phagocytosis assays and studies in xenograft models. The tumor selectivity, mechanism of action, PK properties, side effects, and therapeutic efficacy were further evaluated in humanized (hCD47 and its receptor hSIRPα) immunocompetent syngeneic mouse models.
resultsThe crystal structure reveals that two histidines locate within the CDRs of the light chain directly contribute to the pH-dependent binding of BC31M4. BC31M4 promotes macrophage phagocytosis of tumor cells more potently at acidic-pH than at physiological-pH. Our hCD47/hSIRPα humanized syngeneic mouse model results demonstrated that BC31M4 selectively accumulates in tumors but not in normal tissues. BC31M4 causes minimal side effects and exhibits superior PK properties as compared to the other examined anti-CD47 antibodies. When combined with adoptive T cell transfer, BC31M4 efficiently promotes adaptive immune responses against tumors and also induces immune memory. Moreover, we show that BC31M4's antitumor effects rely on an Fc that mediates strong effector functions.
conclusionsOur study illustrates that the development of a tumor-selective, pH-dependent anti-CD47 antibody safely confers strong therapeutic effects against solid tumors, thus providing a promising therapeutic strategy to overcome the challenges of anti-CD47 therapy.
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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.